Mechanisms of Long Non-Coding RNA in Breast Cancer
Abstract
:1. Introduction
2. Functions of lncRNAs in the Nucleus
2.1. lncRNAs as Regulators of Chromatin Status
HOTAIR
2.2. Enhancer-Like Functions
CCAT1-L
A-ROD
2.3. Regulation of Splicing
2.4. Organization of Nuclear Architecture
3. Functions of lncRNAs in the Cytoplasm
3.1. LncRNAs Acting as miRNA Sponges
Linc-ROR
H19
3.2. LncRNAs Acting as Guide
NORAD
3.3. LncRNA-Encoding Polypeptides
PVT1: One lncRNA, Many Functions
4. Final Remarks
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Volders, P.-J.; Anckaert, J.; Verheggen, K.; Nuytens, J.; Martens, L.; Mestdagh, P.; Vandesompele, J. LNCipedia 5: Towards a reference set of human long non-coding RNAs. Nucleic Acids Res. 2019, 47, D135–D139. [Google Scholar] [CrossRef] [Green Version]
- Gao, Y.; Shang, S.; Guo, S.; Li, X.; Zhou, H.; Liu, H.; Sun, Y.; Wang, J.; Wang, P.; Zhi, H.; et al. Lnc2Cancer 3.0: An updated resource for experimentally supported lncRNA/circRNA cancer associations and web tools based on RNA-seq and scRNA-seq data. Nucleic Acids Res. 2021, 49, D1251–D1258. [Google Scholar] [CrossRef] [PubMed]
- Quek, X.C.; Thomson, D.W.; Maag, J.L.; Bartonicek, N.; Signal, B.; Clark, M.B.; Gloss, B.S.; Dinger, M.E. lncRNAdb v2.0: Expanding the reference database for functional long noncoding RNAs. Nucleic Acids Res. 2015, 43, D168–D173. [Google Scholar] [CrossRef] [PubMed]
- Bao, Z.; Yang, Z.; Huang, Z.; Zhou, Y.; Cui, Q.; Dong, D. LncRNADisease 2.0: An updated database of long non-coding RNA-associated diseases. Nucleic Acids Res. 2019, 47, D1034–D1037. [Google Scholar] [CrossRef] [PubMed]
- Mas-Ponte, D.; Carlevaro-Fita, J.; Palumbo, E.; Pulido, T.H.; Guigo, R.; Johnson, R. LncATLAS database for subcellular localization of long noncoding RNAs. RNA 2017, 23, 1080–1087. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Beermann, J.; Piccoli, M.-T.; Viereck, J.; Thum, T. Non-coding RNAs in Development and Disease: Background, Mechanisms, and Therapeutic Approaches. Physiol. Rev. 2016, 96, 1297–1325. [Google Scholar] [CrossRef] [Green Version]
- Anastasiadou, E.; Jacob, L.S.; Slack, F.J. Non-coding RNA networks in cancer. Nat. Rev. Cancer 2018, 18, 5–18. [Google Scholar] [CrossRef]
- Gupta, R.A.; Shah, N.; Wang, K.C.; Kim, J.; Horlings, H.M.; Wong, D.J.; Tsai, M.-C.; Hung, T.; Argani, P.; Rinn, J.L.; et al. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature 2010, 464, 1071–1076. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yap, K.L.; Li, S.; Muñoz-Cabello, A.M.; Raguz, S.; Zeng, L.; Mujtaba, S.; Gil, J.; Walsh, M.J.; Zhou, M.-M. Molecular Interplay of the Noncoding RNA ANRIL and Methylated Histone H3 Lysine 27 by Polycomb CBX7 in Transcriptional Silencing of INK4a. Mol. Cell 2010, 38, 662–674. [Google Scholar] [CrossRef] [Green Version]
- Kotake, Y.; Nakagawa, T.; Kitagawa, K.; Suzuki, S.; Liu, N.; Kitagawa, M.; Xiong, Y. Long non-coding RNA ANRIL is required for the PRC2 recruitment to and silencing of p15INK4B tumor suppressor gene. Oncogene 2011, 30, 1956–1962. [Google Scholar] [CrossRef] [Green Version]
- Turnbull, C.; Ahmed, S.; Morrison, J.; Pernet, D.; Renwick, A.; Maranian, M.; Seal, S.; Ghoussaini, M.; Hines, S.; Healey, C.S.; et al. Genome-wide association study identifies five new breast cancer susceptibility loci. Nat. Genet. 2010, 42, 504–507. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Xiu, B.; Chi, Y.; Liu, L.; Chi, W.; Zhang, Q.; Chen, J.; Guo, R.; Si, J.; Li, L.; Xue, J.; et al. LINC02273 drives breast cancer metastasis by epigenetically increasing AGR2 transcription. Mol. Cancer 2019, 18, 187. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jones, R.; Wijesinghe, S.; Wilson, C.; Halsall, J.; Liloglou, T.; Kanhere, A. A long intergenic non-coding RNA regulates nuclear localization of DNA methyl transferase-1. Iscience 2021, 24, 102273. [Google Scholar] [CrossRef] [PubMed]
- Pandey, G.K.; Mitra, S.; Subhash, S.; Hertwig, F.; Kanduri, M.; Mishra, K.; Fransson, S.; Ganeshram, A.; Mondal, T.; Bandaru, S.; et al. The Risk-Associated Long Noncoding RNA NBAT-1 Controls Neuroblastoma Progression by Regulating Cell Proliferation and Neuronal Differentiation. Cancer Cell 2014, 26, 722–737. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hu, P.; Chu, J.; Wu, Y.; Sun, L.; Lv, X.; Zhu, Y.; Li, J.; Guo, Q.; Gong, C.; Liu, B.; et al. NBAT1 suppresses breast cancer metastasis by regulating DKK1 via PRC2. Oncotarget 2015, 6, 32410–32425. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tang, T.; Guo, C.; Xia, T.; Zhang, R.; Zen, K.; Pan, Y.; Jin, L. LncCCAT1 Promotes Breast Cancer Stem Cell Function through Activating WNT/beta-catenin Signaling. Theranostics 2019, 9, 7384–7402. [Google Scholar] [CrossRef] [PubMed]
- Ntini, E.; Louloupi, A.; Liz, J.; Muino, J.M.; Marsico, A.; Ørom, U.A.V. Long ncRNA A-ROD activates its target gene DKK1 at its release from chromatin. Nat. Commun. 2018, 9, 1636. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Abdalla, M.O.A.; Yamamoto, T.; Maehara, K.; Nogami, J.; Ohkawa, Y.; Miura, H.; Poonperm, R.; Hiratani, I.; Nakayama, H.; Nakao, M.; et al. The Eleanor ncRNAs activate the topological domain of the ESR1 locus to balance against apoptosis. Nat. Commun. 2019, 10, 3778. [Google Scholar] [CrossRef] [Green Version]
- Fukuoka, M.; Ichikawa, Y.; Osako, T.; Fujita, T.; Baba, S.; Takeuchi, K.; Tsunoda, N.; Ebata, T.; Ueno, T.; Ohno, S.; et al. The ELEANOR noncoding RNA expression contributes to cancer dormancy and predicts late recurrence of estrogen receptor-positive breast cancer. Cancer Sci. 2022, 113, 2336–2351. [Google Scholar] [CrossRef]
- Rossi, T.; Pistoni, M.; Sancisi, V.; Gobbi, G.; Torricelli, F.; Donati, B.; Ribisi, S.; Gugnoni, M.; Ciarrocchi, A. RAIN Is a Novel Enhancer-Associated lncRNA That Controls RUNX2 Expression and Promotes Breast and Thyroid Cancer. Mol. Cancer Res. 2020, 18, 140–152. [Google Scholar] [CrossRef] [Green Version]
- De Troyer, L.; Zhao, P.; Pastor, T.; Baietti, M.F.; Barra, J.; Vendramin, R.; Dok, R.; Lechat, B.; Najm, P.; Van Haver, D.; et al. Stress-induced lncRNA LASTR fosters cancer cell fitness by regulating the activity of the U4/U6 recycling factor SART3. Nucleic Acids Res. 2020, 48, 2502–2517. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Beltran, M.; Puig, I.; Peña, C.; García, J.M.; Álvarez, A.B.; Peña, R.; Bonilla, F.; de Herreros, A.G. A natural antisense transcript regulates Zeb2/Sip1 gene expression during Snail1-induced epithelial-mesenchymal transition. Genes Dev. 2008, 22, 756–769. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Singh, R.; Gupta, S.C.; Peng, W.-X.; Zhou, N.; Pochampally, R.; Atfi, A.; Watabe, K.; Lu, Z.; Mo, Y.-Y. Regulation of alternative splicing of Bcl-x by BC200 contributes to breast cancer pathogenesis. Cell Death Dis. 2016, 7, e2262. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Shin, V.Y.; Chen, J.; Cheuk, I.W.-Y.; Siu, M.-T.; Ho, C.-W.; Wang, X.; Jin, H.; Kwong, A. Long non-coding RNA NEAT1 confers oncogenic role in triple-negative breast cancer through modulating chemoresistance and cancer stemness. Cell Death Dis. 2019, 10, 270. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kim, J.; Piao, H.-L.; Kim, B.-J.; Yao, F.; Han, Z.; Wang, Y.; Xiao, Z.; Siverly, A.N.; Lawhon, S.E.; Ton, B.N.; et al. Long noncoding RNA MALAT1 suppresses breast cancer metastasis. Nat. Genet. 2018, 50, 1705–1715. [Google Scholar] [CrossRef]
- Arun, G.; Diermeier, S.; Akerman, M.; Chang, K.-C.; Wilkinson, J.E.; Hearn, S.; Kim, Y.; MacLeod, A.R.; Krainer, A.R.; Norton, L.; et al. Differentiation of mammary tumors and reduction in metastasis upon Malat1 lncRNA loss. Genes Dev. 2016, 30, 34–51. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Richart, L.; Picod-Chedotel, M.-L.; Wassef, M.; Macario, M.; Aflaki, S.; Salvador, M.A.; Héry, T.; Dauphin, A.; Wicinski, J.; Chevrier, V.; et al. XIST loss impairs mammary stem cell differentiation and increases tumorigenicity through Mediator hyperactivation. Cell 2022, 185, 2164–2183.e25. [Google Scholar] [CrossRef] [PubMed]
- Noh, J.H.; Kim, K.M.; Abdelmohsen, K.; Yoon, J.-H.; Panda, A.C.; Munk, R.; Kim, J.; Curtis, J.; Moad, C.A.; Wohler, C.M.; et al. HuR and GRSF1 modulate the nuclear export and mitochondrial localization of the lncRNARMRP. Genes Dev. 2016, 30, 1224–1239. [Google Scholar] [CrossRef] [Green Version]
- Wang, Y.; Wu, S.; Zhu, X.; Zhang, L.; Deng, J.; Li, F.; Guo, B.; Zhang, S.; Wu, R.; Zhang, Z.; et al. LncRNA-encoded polypeptide ASRPS inhibits triple-negative breast cancer angiogenesis. J. Exp. Med. 2020, 217, e20190950. [Google Scholar] [CrossRef]
- Matsumoto, A.; Pasut, A.; Matsumoto, M.; Yamashita, R.; Fung, J.; Monteleone, E.; Saghatelian, A.; Nakayama, K.I.; Clohessy, J.G.; Pandolfi, P.P. mTORC1 and muscle regeneration are regulated by the LINC00961-encoded SPAR polypeptide. Nature 2017, 541, 228–232. [Google Scholar] [CrossRef]
- Guo, B.; Wu, S.; Zhu, X.; Zhang, L.; Deng, J.; Li, F.; Wang, Y.; Zhang, S.; Wu, R.; Lu, J.; et al. Micropeptide CIP 2A-BP encoded by LINC 00665 inhibits triple-negative breast cancer progression. EMBO J. 2019, 39, e102190. [Google Scholar] [CrossRef] [PubMed]
- Rossi, M.; Bucci, G.; Rizzotto, D.; Bordo, D.; Marzi, M.J.; Puppo, M.; Flinois, A.; Spadaro, D.; Citi, S.; Emionite, L.; et al. LncRNA EPR controls epithelial proliferation by coordinating Cdkn1a transcription and mRNA decay response to TGF-beta. Nat. Commun. 2019, 10, 1969. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Anderson, D.M.; Anderson, K.M.; Chang, C.-L.; Makarewich, C.A.; Nelson, B.R.; McAnally, J.R.; Kasaragod, P.; Shelton, J.M.; Liou, J.; Bassel-Duby, R.; et al. A Micropeptide Encoded by a Putative Long Noncoding RNA Regulates Muscle Performance. Cell 2015, 160, 595–606. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Huang, J.-Z.; Chen, M.; Chen, D.; Gao, X.-C.; Zhu, S.; Huang, H.; Hu, M.; Zhu, H.; Yan, G.-R. A Peptide Encoded by a Putative lncRNA HOXB-AS3 Suppresses Colon Cancer Growth. Mol. Cell 2017, 68, 171–184.e6. [Google Scholar] [CrossRef] [Green Version]
- Grelet, S.; Link, L.A.; Howley, B.; Obellianne, C.; Palanisamy, V.; Gangaraju, V.K.; Diehl, J.A.; Howe, P.H. A regulated PNUTS mRNA to lncRNA splice switch mediates EMT and tumour progression. Nature 2017, 19, 1105–1115. [Google Scholar] [CrossRef] [Green Version]
- Hou, P.; Zhao, Y.; Li, Z.; Yao, R.; Ma, M.; Gao, Y.; Zhao, L.; Zhang, Y.; Huang, B.; Lu, J. LincRNA-ROR induces epithelial-to-mesenchymal transition and contributes to breast cancer tumorigenesis and metastasis. Cell. Death Dis. 2014, 5, e1287. [Google Scholar] [CrossRef] [Green Version]
- Zhou, Q.; Guo, J.; Huang, W.; Yu, X.; Xu, C.; Long, X. Linc-ROR promotes the progression of breast cancer and decreases the sensitivity to rapamycin through miR-194-3p targeting MECP2. Mol. Oncol. 2020, 14, 2231–2250. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Vennin, C.; Spruyt, N.; Dahmani, F.; Julien, S.; Bertucci, F.; Finetti, P.; Chassat, T.; Bourette, R.P.; Le Bourhis, X.; Adriaenssens, E. H19 non coding RNA-derived miR-675 enhances tumorigenesis and metastasis of breast cancer cells by downregulating c-Cbl and Cbl-b. Oncotarget 2015, 6, 29209–29223. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wang, M.; Li, Y.; Xiao, G.-D.; Zheng, X.-Q.; Wang, J.-C.; Xu, C.-W.; Qin, S.; Ren, H.; Tang, S.-C.; Sun, X. H19 regulation of oestrogen induction of symmetric division is achieved by antagonizing Let-7c in breast cancer stem-like cells. Cell Prolif. 2019, 52, e12534. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Peng, F.; Li, T.T.; Wang, K.L.; Xiao, G.Q.; Wang, J.H.; Zhao, H.D.; Kang, Z.J.; Fan, W.J.; Zhu, L.L.; Li, M.; et al. H19/let-7/LIN28 reciprocal negative regulatory circuit promotes breast cancer stem cell maintenance. Cell Death Dis. 2017, 8, e2569. [Google Scholar] [CrossRef] [Green Version]
- Yuan, J.H.; Yang, F.; Wang, F.; Ma, J.Z.; Guo, Y.J.; Tao, Q.F.; Liu, F.; Pan, W.; Wang, T.T.; Zhou, C.C.; et al. A long noncoding RNA activated by TGF-beta promotes the invasion-metastasis cascade in hepatocellular carcinoma. Cancer Cell 2014, 25, 666–681. [Google Scholar] [CrossRef] [Green Version]
- Li, R.-H.; Chen, M.; Liu, J.; Shao, C.-C.; Guo, C.-P.; Wei, X.-L.; Li, Y.-C.; Huang, W.-H.; Zhang, G.-J. Long noncoding RNA ATB promotes the epithelial−mesenchymal transition by upregulating the miR-200c/Twist1 axe and predicts poor prognosis in breast cancer. Cell Death Dis. 2018, 9, 1171. [Google Scholar] [CrossRef] [Green Version]
- Wang, Q.; Li, G.; Ma, X.; Liu, L.; Liu, J.; Yin, Y.; Li, H.; Chen, Y.; Zhang, X.; Zhang, L.; et al. LncRNA TINCR impairs the efficacy of immunotherapy against breast cancer by recruiting DNMT1 and downregulating MiR-199a-5p via the STAT1–TINCR-USP20-PD-L1 axis. Cell Death Dis. 2023, 14, 76. [Google Scholar] [CrossRef]
- Han, L.; Yan, Y.; Zhao, L.; Liu, Y.; Lv, X.; Zhang, L.; Zhao, Y.; Zhao, H.; He, M.; Wei, M. LncRNA HOTTIP facilitates the stemness of breast cancer via regulation of miR-148a-3p/WNT1 pathway. J. Cell. Mol. Med. 2020, 24, 6242–6252. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Qiao, Y.; Jin, T.; Guan, S.; Cheng, S.; Wen, S.; Zeng, H.; Zhao, M.; Yang, L.; Wan, X.; Qiu, Y.; et al. Long non-coding RNA Lnc-408 promotes invasion and metastasis of breast cancer cell by regulating LIMK1. Oncogene 2021, 40, 4198–4213. [Google Scholar] [CrossRef] [PubMed]
- Han, J.; Chen, X.; Wang, J.; Bin Liu, B. Glycolysis-related lncRNA TMEM105 upregulates LDHA to facilitate breast cancer liver metastasis via sponging miR-1208. Cell Death Dis. 2023, 14, 80. [Google Scholar] [CrossRef]
- Jadaliha, M.; Gholamalamdari, O.; Tang, W.; Zhang, Y.; Petracovici, A.; Hao, Q.; Tariq, A.; Kim, T.G.; Holton, S.E.; Singh, D.K.; et al. A natural antisense lncRNA controls breast cancer progression by promoting tumor suppressor gene mRNA stability. PLOS Genet. 2018, 14, e1007802. [Google Scholar] [CrossRef] [PubMed]
- Huang, D.; Chen, J.; Yang, L.; Ouyang, Q.; Li, J.; Lao, L.; Zhao, J.; Liu, J.; Lu, Y.; Xing, Y.; et al. NKILA lncRNA promotes tumor immune evasion by sensitizing T cells to activation-induced cell death. Nat. Immunol. 2018, 19, 1112–1125. [Google Scholar] [CrossRef]
- Kretz, M.; Siprashvili, Z.; Chu, C.; Webster, D.E.; Zehnder, A.; Qu, K.; Lee, C.S.; Flockhart, R.J.; Groff, A.F.; Chow, J.; et al. Control of somatic tissue differentiation by the long non-coding RNA TINCR. Nature 2012, 493, 231–235. [Google Scholar] [CrossRef] [Green Version]
- Sharma, U.; Barwal, T.S.; Malhotra, A.; Pant, N.; Vivek; Dey, D.; Gautam, A.; Tuli, H.S.; Vasquez, K.M.; Jain, A. Long non-coding RNA TINCR as potential biomarker and therapeutic target for cancer. Life Sci. 2020, 257, 118035. [Google Scholar] [CrossRef]
- Lee, S.; Kopp, F.; Chang, T.-C.; Sataluri, A.; Chen, B.; Sivakumar, S.; Yu, H.; Xie, Y.; Mendell, J.T. Noncoding RNA NORAD Regulates Genomic Stability by Sequestering PUMILIO Proteins. Cell 2015, 164, 69–80. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tan, B.-S.; Yang, M.-C.; Singh, S.; Chou, Y.-C.; Chen, H.-Y.; Wang, M.-Y.; Wang, Y.-C.; Chen, R.-H. LncRNA NORAD is repressed by the YAP pathway and suppresses lung and breast cancer metastasis by sequestering S100P. Oncogene 2019, 38, 5612–5626. [Google Scholar] [CrossRef] [PubMed]
- Liu, J.; Lao, L.; Chen, J.; Li, J.; Zeng, W.; Zhu, X.; Li, J.; Chen, X.; Yang, L.; Xing, Y.; et al. The IRENA lncRNA converts chemotherapy-polarized tumor-suppressing macrophages to tumor-promoting phenotypes in breast cancer. Nat. Cancer 2021, 2, 457–473. [Google Scholar] [CrossRef] [PubMed]
- Guo, W.; Li, J.; Huang, H.; Fu, F.; Lin, Y.; Wang, C. LncRNA PCIR Is an Oncogenic Driver via Strengthen the Binding of TAB3 and PABPC4 in Triple Negative Breast Cancer. Front. Oncol. 2021, 11, 630300. [Google Scholar] [CrossRef]
- Lin, A.; Li, C.; Xing, Z.; Hu, Q.; Liang, K.; Han, L.; Wang, C.; Hawke, D.H.; Wang, S.; Zhang, Y.; et al. The LINK-A lncRNA activates normoxic HIF1α signalling in triple-negative breast cancer. Nature 2016, 18, 213–224. [Google Scholar] [CrossRef]
- Lin, X.; Dinglin, X.; Cao, S.; Zheng, S.; Wu, C.; Chen, W.; Li, Q.; Hu, Q.; Zheng, F.; Wu, Z.; et al. Enhancer-Driven lncRNA BDNF-AS Induces Endocrine Resistance and Malignant Progression of Breast Cancer through the RNH1/TRIM21/mTOR Cascade. Cell Rep. 2020, 31, 107753. [Google Scholar] [CrossRef]
- Leucci, E.; Vendramin, R.; Spinazzi, M.; Laurette, P.; Fiers, M.; Wouters, J.; Radaelli, E.; Eyckerman, S.; Leonelli, C.; Vanderheyden, K.; et al. Melanoma addiction to the long non-coding RNA SAMMSON. Nature 2016, 531, 518–522. [Google Scholar] [CrossRef]
- Vendramin, R.; Verheyden, Y.; Ishikawa, H.; Goedert, L.; Nicolas, E.; Saraf, K.; Armaos, A.; Ponti, R.D.; Izumikawa, K.; Mestdagh, P.; et al. SAMMSON fosters cancer cell fitness by concertedly enhancing mitochondrial and cytosolic translation. Nat. Struct. Mol. Biol. 2018, 25, 1035–1046. [Google Scholar] [CrossRef]
- Sang, L.; Ju, H.-Q.; Yang, Z.; Ge, Q.; Zhang, Z.; Liu, F.; Yang, L.; Gong, H.; Shi, C.; Qu, L.; et al. Mitochondrial long non-coding RNA GAS5 tunes TCA metabolism in response to nutrient stress. Nat. Metab. 2021, 3, 90–106. [Google Scholar] [CrossRef] [PubMed]
- Guo, C.-J.; Ma, X.-K.; Xing, Y.-H.; Zheng, C.-C.; Xu, Y.-F.; Shan, L.; Zhang, J.; Wang, S.; Wang, Y.; Carmichael, G.G.; et al. Distinct Processing of lncRNAs Contributes to Non-conserved Functions in Stem Cells. Cell 2020, 181, 621–636.e22. [Google Scholar] [CrossRef]
- Derrien, T.; Johnson, R.; Bussotti, G.; Tanzer, A.; Djebali, S.; Tilgner, H.; Guernec, G.; Martin, D.; Merkel, A.; Knowles, D.G.; et al. The GENCODE v7 Catalog of Human Long Noncoding RNAs: Analysis of Their Gene Structure, Evolution, and Expression. Genome Res. 2012, 22, 1775–1789. [Google Scholar] [CrossRef] [Green Version]
- Schlackow, M.; Nojima, T.; Gomes, T.; Dhir, A.; Carmo-Fonseca, M.; Proudfoot, N.J. Distinctive Patterns of Transcription and RNA Processing for Human lincRNAs. Mol. Cell 2017, 65, 25–38. [Google Scholar] [CrossRef] [Green Version]
- Lubelsky, Y.; Ulitsky, I. Sequences enriched in Alu repeats drive nuclear localization of long RNAs in human cells. Nature 2018, 555, 107–111. [Google Scholar] [CrossRef]
- Kopp, F.; Mendell, J.T. Functional Classification and Experimental Dissection of Long Noncoding RNAs. Cell 2018, 172, 393–407. [Google Scholar] [CrossRef] [Green Version]
- Statello, L.; Guo, C.-J.; Chen, L.-L.; Huarte, M. Gene regulation by long non-coding RNAs and its biological functions. Nat. Rev. Mol. Cell Biol. 2021, 22, 96–118. [Google Scholar] [CrossRef]
- Böhmdorfer, G.; Wierzbicki, A.T. Control of Chromatin Structure by Long Noncoding RNA. Trends Cell Biol. 2015, 25, 623–632. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Qu, X.; Alsager, S.; Zhuo, Y.; Shan, B. HOX transcript antisense RNA (HOTAIR) in cancer. Cancer Lett. 2019, 454, 90–97. [Google Scholar] [CrossRef] [PubMed]
- Shah, N.; Sukumar, S. The Hox genes and their roles in oncogenesis. Nat. Rev. Cancer 2010, 10, 361–371. [Google Scholar] [CrossRef] [PubMed]
- He, S.; Liu, S.; Zhu, H. The sequence, structure and evolutionary features of HOTAIR in mammals. BMC Evol. Biol. 2011, 11, 102. [Google Scholar] [CrossRef] [Green Version]
- Rinn, J.L.; Kertesz, M.; Wang, J.K.; Squazzo, S.L.; Xu, X.; Brugmann, S.A.; Goodnough, L.H.; Helms, J.A.; Farnham, P.J.; Segal, E.; et al. Functional Demarcation of Active and Silent Chromatin Domains in Human HOX Loci by Noncoding RNAs. Cell 2007, 129, 1311–1323. [Google Scholar] [CrossRef] [Green Version]
- Wang, L.; Zeng, X.; Chen, S.; Ding, L.; Zhong, J.; Zhao, J.C.; Wang, L.; Sarver, A.; Koller, A.; Zhi, J.; et al. BRCA1 is a negative modulator of the PRC2 complex. EMBO J. 2013, 32, 1584–1597. [Google Scholar] [CrossRef] [Green Version]
- Gasperini, M.; Tome, J.M.; Shendure, J. Towards a comprehensive catalogue of validated and target-linked human enhancers. Nat. Rev. Genet. 2020, 21, 292–310. [Google Scholar] [CrossRef] [PubMed]
- Andersson, R.; Sandelin, A. Determinants of enhancer and promoter activities of regulatory elements. Nat. Rev. Genet. 2020, 21, 71–87. [Google Scholar] [CrossRef] [PubMed]
- Li, W.; Notani, D.; Rosenfeld, W.L.D.N.M.G. Enhancers as non-coding RNA transcription units: Recent insights and future perspectives. Nat. Rev. Genet. 2016, 17, 207–223. [Google Scholar] [CrossRef]
- Xiang, J.F.; Yin, Q.F.; Chen, T.; Zhang, Y.; Zhang, X.O.; Wu, Z.; Zhang, S.; Wang, H.B.; Ge, J.; Lu, X.; et al. Human colorectal cancer-specific CCAT1-L lncRNA regulates long-range chromatin interactions at the MYC locus. Cell Res. 2014, 24, 513–531. [Google Scholar] [CrossRef] [Green Version]
- Vučićević, D.; Corradin, O.; Ntini, E.; Scacheri, P.C.; Ørom, U.A. Long ncRNA expression associates with tissue-specific enhancers. Cell Cycle 2015, 14, 253–260. [Google Scholar] [CrossRef] [Green Version]
- Pomerantz, M.M.; Ahmadiyeh, N.; Jia, L.; Herman, P.; Verzi, M.P.; Doddapaneni, H.; Beckwith, C.A.; Chan, J.A.; Hills, A.; Davis, M.; et al. The 8q24 cancer risk variant rs6983267 shows long-range interaction with MYC in colorectal cancer. Nat. Genet. 2009, 41, 882–884. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tuupanen, S.; Turunen, M.; Lehtonen, R.; Hallikas, O.; Vanharanta, S.; Kivioja, T.; Björklund, M.; Wei, G.; Yan, J.; Niittymäki, I.; et al. The common colorectal cancer predisposition SNP rs6983267 at chromosome 8q24 confers potential to enhanced Wnt signaling. Nat. Genet. 2009, 41, 885–890. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kim, Y.; Yu, H. Shaping of the 3D genome by the ATPase machine cohesin. Exp. Mol. Med. 2020, 52, 1891–1897. [Google Scholar] [CrossRef] [PubMed]
- Lai, Y.; Chen, Y.; Lin, Y.; Ye, L. Down-regulation of LncRNA CCAT1 enhances radiosensitivity via regulating miR-148b in breast cancer. Cell Biol. Int. 2018, 42, 227–236. [Google Scholar] [CrossRef] [PubMed]
- Qiao, L.; Xu, Z.-L.; Zhao, T.-J.; Ye, L.-H.; Zhang, X.-D. Dkk-1 secreted by mesenchymal stem cells inhibits growth of breast cancer cells via depression of Wnt signalling. Cancer Lett. 2008, 269, 67–77. [Google Scholar] [CrossRef] [PubMed]
- Tan, J.Y.; Biasini, A.; Young, R.S.; Marques, A.C. Splicing of enhancer-associated lincRNAs contributes to enhancer activity. Life Sci. Alliance 2020, 3, e202000663. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gil, N.; Ulitsky, I. Production of Spliced Long Noncoding RNAs Specifies Regions with Increased Enhancer Activity. Cell Syst. 2018, 7, 537–547.e3. [Google Scholar] [CrossRef] [Green Version]
- Kitamura, K.; Nimura, K. Regulation of RNA Splicing: Aberrant Splicing Regulation and Therapeutic Targets in Cancer. Cells 2021, 10, 923. [Google Scholar] [CrossRef]
- Rader, S.D.; Guthrie, C. A conserved Lsm-interaction motif in Prp24 required for efficient U4/U6 di-snRNP formation. RNA 2002, 8, 1378–1392. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jacob, A.G.; Smith, C.W. Intron retention as a component of regulated gene expression programs. Hum. Genet. 2017, 136, 1043–1057. [Google Scholar] [CrossRef] [Green Version]
- Memon, D.; Dawson, K.; Smowton, C.S.; Xing, W.; Dive, C.; Miller, C.J. Hypoxia-driven splicing into noncoding isoforms regulates the DNA damage response. NPJ Genom. Med. 2016, 1, 16020. [Google Scholar] [CrossRef] [Green Version]
- Quinodoz, S.A.; Jachowicz, J.W.; Bhat, P.; Ollikainen, N.; Banerjee, A.K.; Goronzy, I.N.; Blanco, M.R.; Chovanec, P.; Chow, A.; Markaki, Y.; et al. RNA promotes the formation of spatial compartments in the nucleus. Cell 2021, 184, 5775–5790.e30. [Google Scholar] [CrossRef] [PubMed]
- West, J.A.; Davis, C.P.; Sunwoo, H.; Simon, M.D.; Sadreyev, R.I.; Wang, P.I.; Tolstorukov, M.Y.; Kingston, R.E. The Long Noncoding RNAs NEAT1 and MALAT1 Bind Active Chromatin Sites. Mol. Cell 2014, 55, 791–802. [Google Scholar] [CrossRef] [Green Version]
- Yamazaki, T.; Souquere, S.; Chujo, T.; Kobelke, S.; Chong, Y.S.; Fox, A.H.; Bond, C.S.; Nakagawa, S.; Pierron, G.; Hirose, T. Functional Domains of NEAT1 Architectural lncRNA Induce Paraspeckle Assembly through Phase Separation. Mol. Cell 2018, 70, 1038–1053.e7. [Google Scholar] [CrossRef] [Green Version]
- Dong, P.; Xiong, Y.; Yue, J.; Hanley, S.J.B.; Kobayashi, N.; Todo, Y.; Watari, H. Long Non-coding RNA NEAT1: A Novel Target for Diagnosis and Therapy in Human Tumors. Front. Genet. 2018, 9, 471. [Google Scholar] [CrossRef] [Green Version]
- Pang, Y.; Wu, J.; Li, X.; Wang, C.; Wang, M.; Liu, J.; Yang, G. NEAT1/miR-124/STAT3 feedback loop promotes breast cancer progression. Int. J. Oncol. 2019, 55, 745–754. [Google Scholar] [CrossRef] [PubMed]
- Johnsson, P.; Lipovich, L.; Grandér, D.; Morris, K.V. Evolutionary conservation of long non-coding RNAs; sequence, structure, function. Biochim. et Biophys. Acta (BBA) -Gen. Subj. 2014, 1840, 1063–1071. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bernard, D.; Prasanth, K.V.; Tripathi, V.; Colasse, S.; Nakamura, T.; Xuan, Z.; Zhang, M.Q.; Sedel, F.; Jourdren, L.; Coulpier, F.; et al. A long nuclear-retained non-coding RNA regulates synaptogenesis by modulating gene expression. EMBO J. 2010, 29, 3082–3093. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tripathi, V.; Ellis, J.D.; Shen, Z.; Song, D.Y.; Pan, Q.; Watt, A.T.; Freier, S.M.; Bennett, C.F.; Sharma, A.; Bubulya, P.A.; et al. The Nuclear-Retained Noncoding RNA MALAT1 Regulates Alternative Splicing by Modulating SR Splicing Factor Phosphorylation. Mol. Cell 2010, 39, 925–938. [Google Scholar] [CrossRef] [Green Version]
- Yu, J.; Jin, T.; Zhang, T. Suppression of Long Non-Coding RNA Metastasis-Associated Lung Adenocarcinoma Transcript 1 (MALAT1) Potentiates Cell Apoptosis and Drug Sensitivity to Taxanes and Adriamycin in Breast Cancer. Experiment 2020, 26, e922672. [Google Scholar] [CrossRef]
- Menghi, F.; Barthel, F.P.; Yadav, V.; Tang, M.; Ji, B.; Tang, Z.; Carter, G.W.; Ruan, Y.; Scully, R.; Verhaak, R.G.; et al. The Tandem Duplicator Phenotype Is a Prevalent Genome-Wide Cancer Configuration Driven by Distinct Gene Mutations. Cancer Cell 2018, 34, 197–210.e5. [Google Scholar] [CrossRef]
- Zuckerman, B.; Ron, M.; Mikl, M.; Segal, E.; Ulitsky, I. Gene Architecture and Sequence Composition Underpin Selective Dependency of Nuclear Export of Long RNAs on NXF1 and the TREX Complex. Mol. Cell 2020, 79, 251–267.e6. [Google Scholar] [CrossRef]
- Szostak, N.; Royo, F.; Rybarczyk, A.; Szachniuk, M.; Blazewicz, J.; Del Sol, A.; Falcon-Perez, J.M. Sorting signal targeting mRNA into hepatic extracellular vesicles. RNA Biol. 2014, 11, 836–844. [Google Scholar] [CrossRef] [Green Version]
- Denzler, R.; Agarwal, V.; Stefano, J.; Bartel, D.P.; Stoffel, M. Assessing the ceRNA Hypothesis with Quantitative Measurements of miRNA and Target Abundance. Mol. Cell 2014, 54, 766–776. [Google Scholar] [CrossRef] [Green Version]
- Wang, Y.; Xu, Z.; Jiang, J.; Xu, C.; Kang, J.; Xiao, L.; Wu, M.; Xiong, J.; Guo, X.; Liu, H. Endogenous miRNA sponge lincRNA-RoR regulates Oct4, Nanog, and Sox2 in human embryonic stem cell self-renewal. Dev. Cell 2013, 25, 69–80. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Peng, W.X.; Huang, J.G.; Yang, L.; Gong, A.H.; Mo, Y.Y. Linc-RoR promotes MAPK/ERK signaling and confers estrogen-independent growth of breast cancer. Mol. Cancer 2017, 16, 161. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gabory, A.; Ripoche, M.-A.; Le Digarcher, A.; Watrin, F.; Ziyyat, A.; Forné, T.; Jammes, H.; Ainscough, J.F.X.; Surani, M.A.; Journot, L.; et al. H19 acts as a trans regulator of the imprinted gene network controlling growth in mice. Development 2009, 136, 3413–3421. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Keniry, A.; Oxley, D.; Monnier, P.; Kyba, M.; Dandolo, L.; Smits, G.; Reik, W. The H19 lincRNA is a developmental reservoir of miR-675 that suppresses growth and Igf1r. Nature 2012, 14, 659–665. [Google Scholar] [CrossRef] [Green Version]
- Kallen, A.N.; Zhou, X.-B.; Xu, J.; Qiao, C.; Ma, J.; Yan, L.; Lu, L.; Liu, C.; Yi, J.-S.; Zhang, H.; et al. The Imprinted H19 LncRNA Antagonizes Let-7 MicroRNAs. Mol. Cell 2013, 52, 101–112. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Peng, F.; Wang, J.-H.; Fan, W.-J.; Meng, Y.-T.; Li, M.-M.; Li, T.-T.; Cui, B.; Wang, H.-F.; Zhao, Y.; An, F.; et al. Glycolysis gatekeeper PDK1 reprograms breast cancer stem cells under hypoxia. Oncogene 2018, 37, 1062–1074. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Munschauer, M.; Nguyen, C.T.; Sirokman, K.; Hartigan, C.R.; Hogstrom, L.; Engreitz, J.M.; Ulirsch, J.C.; Fulco, C.P.; Subramanian, V.; Chen, J.; et al. The NORAD lncRNA assembles a topoisomerase complex critical for genome stability. Nature 2018, 561, 132–136. [Google Scholar] [CrossRef] [Green Version]
- Shtivelman, E.; Bishop, J.M. Effects of translocations on transcription from PVT. Mol. Cell. Biol. 1990, 10, 1835–1839. [Google Scholar] [CrossRef]
- Huppi, K.; Siwarski, D. Chimeric transcripts with an open reading frame are generated as a result of translocation to thePvt-1 region in mouse B-cell tumors. Int. J. Cancer 1994, 59, 848–851. [Google Scholar] [CrossRef]
- Cho, S.W.; Xu, J.; Sun, R.; Mumbach, M.R.; Carter, A.C.; Chen, Y.G.; Yost, K.E.; Kim, J.; He, J.; Nevins, S.A.; et al. Promoter of lncRNA Gene PVT1 Is a Tumor-Suppressor DNA Boundary Element. Cell 2018, 173, 1398–1412.e22. [Google Scholar] [CrossRef] [Green Version]
- Curtis, C.; Shah, S.P.; Chin, S.-F.; Turashvili, G.; Palacio, O.R.; Dunning, M.; Speed, D.; Lynch, A.; Samarajiwa, S.; Yuan, Y.; et al. The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups. Nature 2020, 486, 346–352. [Google Scholar] [CrossRef] [PubMed]
- Liu, S.; Chen, W.; Hu, H.; Zhang, T.; Wu, T.; Li, X.; Li, Y.; Kong, Q.; Lu, H.; Lu, Z. Long noncoding RNA PVT1 promotes breast cancer proliferation and metastasis by binding miR-128-3p and UPF1. Breast Cancer Res. 2021, 23, 115. [Google Scholar] [CrossRef] [PubMed]
- Guan, Y.; Kuo, W.-L.; Stilwell, J.L.; Takano, H.; Lapuk, A.V.; Fridlyand, J.; Mao, J.-H.; Yu, M.; Miller, M.A.; Santos, J.L.; et al. Amplification of PVT1 Contributes to the Pathophysiology of Ovarian and Breast Cancer. Clin. Cancer Res. 2007, 13, 5745–5755. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yan, C.; Chen, Y.; Kong, W.; Fu, L.; Liu, Y.; Yao, Q.; Yuan, Y. PVT1-derived miR-1207-5p promotes breast cancer cell growth by targeting STAT6. Cancer Sci. 2017, 108, 868–876. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Xu, J.; Gu, X.; Yang, X.; Meng, Y. MiR-1204 promotes ovarian squamous cell carcinoma growth by increasing glucose uptake. Biosci. Biotechnol. Biochem. 2019, 83, 123–128. [Google Scholar] [CrossRef] [PubMed]
- Wang, Y.; Li, X.; Liu, W.; Li, B.; Chen, D.; Hu, F.; Wang, L.; Liu, X.M.; Cui, R.; Liu, R. MicroRNA-1205, encoded on chromosome 8q24, targets EGLN3 to induce cell growth and contributes to risk of castration-resistant prostate cancer. Oncogene 2019, 38, 4820–4834. [Google Scholar] [CrossRef]
- You, L.; Wang, H.; Yang, G.; Zhao, F.; Zhang, J.; Liu, Z.; Zhang, T.; Liang, Z.; Liu, C.; Zhao, Y. Gemcitabine exhibits a suppressive effect on pancreatic cancer cell growth by regulating processing of PVT 1 to miR1207. Mol. Oncol. 2018, 12, 2147–2164. [Google Scholar] [CrossRef] [Green Version]
- Das, D.K.; Ogunwobi, O.O. A novel microRNA-1207-3p/FNDC1/FN1/AR regulatory pathway in prostate cancer. RNA Dis. 2017, 4, e1503. [Google Scholar]
- Wang, W.; Zhou, R.; Wu, Y.; Liu, Y.; Su, W.; Xiong, W.; Zeng, Z. PVT1 Promotes Cancer Progression via MicroRNAs. Front. Oncol. 2019, 9, 609. [Google Scholar] [CrossRef] [Green Version]
- Wu, X.-Z.; Cui, H.-P.; Lv, H.-J.; Feng, L. Knockdown of lncRNA PVT1 inhibits retinoblastoma progression by sponging miR-488-3p. Biomed. Pharmacother. 2019, 112, 108627. [Google Scholar] [CrossRef]
- Hua, X.; Xiao, Y.; Pan, W.; Li, M.; Huang, X.; Liao, Z.; Xian, Q.; Yu, L. miR-186 inhibits cell proliferation of prostate cancer by targeting GOLPH3. Am. J. Cancer Res. 2016, 6, 1650–1660. [Google Scholar] [PubMed]
- Tseng, Y.Y.; Moriarity, B.S.; Gong, W.; Akiyama, R.; Tiwari, A.; Kawakami, H.; Ronning, P.; Reuland, B.; Guenther, K.; Beadnell, T.C.; et al. PVT1 dependence in cancer with MYC copy-number increase. Nature 2014, 512, 82–86. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Carramusa, L.; Contino, F.; Ferro, A.; Minafra, L.; Perconti, G.; Giallongo, A.; Feo, S. The PVT-1 oncogene is a Myc protein target that is overexpressed in transformed cells. J. Cell. Physiol. 2007, 213, 511–518. [Google Scholar] [CrossRef] [PubMed]
- Nik-Zainal, S.; Davies, H.; Staaf, J.; Ramakrishna, M.; Glodzik, D.; Zou, X.; Martincorena, I.; Alexandrov, L.B.; Martin, S.; Wedge, D.C.; et al. Landscape of somatic mutations in 560 breast cancer whole-genome sequences. Nature 2016, 534, 47–54. [Google Scholar] [CrossRef] [Green Version]
- Oh, S.; Shao, J.; Mitra, J.; Xiong, F.; D’Antonio, M.; Wang, R.; Garcia-Bassets, I.; Ma, Q.; Zhu, X.; Lee, J.-H.; et al. Enhancer release and retargeting activates disease-susceptibility genes. Nature 2021, 595, 735–740. [Google Scholar] [CrossRef]
- Olivero, C.E.; Martínez-Terroba, E.; Zimmer, J.; Liao, C.; Tesfaye, E.; Hooshdaran, N.; Schofield, J.; Bendor, J.; Fang, D.; Simon, M.D.; et al. p53 Activates the Long Noncoding RNA Pvt1b to Inhibit Myc and Suppress Tumorigenesis. Mol. Cell 2020, 77, 761–774.e8. [Google Scholar] [CrossRef]
Function | Name | Mechanism | Cell Model |
---|---|---|---|
Chromatin Regulation | HOTAIR [8] | HOTAIR functions as a scaffold for the repression of the HOX gene cluster. In breast cancer, the increased expression of the transcript causes the re-targeting of PRC2 and boosts invasion and metastasis. | BC cell lines (MDA-MB-231, SK-BR-3, MCF-10A, MCF-7, HCC1954, T47D and MDA-MB-453) |
ANRIL [9,10,11] | ANRIL is transcribed antisense to the INK4/ARF locus containing multiple tumor-suppressing genes responsible for the negative regulation of cell cycle progression. The transcript coordinates in cis the epigenetic repression of the locus that is mediated by PRC1 and PRC2. The ANRIL locus bears disease-susceptibility polymorphisms for breast cancer. | Primary samples of breast cancer patients | |
LINC02273 [12] | Regulates the activating epigenetic markers H3K4me3 and H3K27ac in the promoter of the AGR2 oncogene, promoting breast cancer metastasis. | Primary samples of metastatic lymph nodes of breast cancer patients and BC cell lines | |
CCDC26 [13] | Regulates DNMT1 nuclear localization and DNA methylation. Downregulation of this lncRNA is associated with increased double-strand breaks. | Acute myeloid leukemia | |
NBAT-1 [14,15] | Tumor-suppressing lncRNA interacts with PRC2 to realize the epigenetic repression of genes involved in cell proliferation, invasion and migration. | Neuroblastoma and breast cancer | |
Enhancer-like functions | CCAT1L [16] | CCAT1L establishes a long-range interaction bridging the oncogene MYC with its enhancers. | BC primary samples and cell lines |
A-ROD [17] | The A-ROD mature transcript allows long-range interaction occurring between DKK1 and its upstream enhancer. | MCF-7 and MDA-MB-231 | |
Eleanor [18,19] | Enables the formation of a TAD that supports the expression of the ESR1 gene and regulates the interaction with a secondary TAD containing the FOXA1 gene, a regulator of apoptosis. | Estrogen receptor positive primary samples and MCF7-LTED (model for long-term estrogen deprivation) | |
RAIN [20] | Enhancer-transcribed lncRNA associates with the WDR5 complex, favoring Pol2 transcription at the nearby RUNX2 promoter, leading to the activation of the downstream oncogenic transcription factors and associated features. | Thyroid and breast cancer. Breast cancer cell lines (MCF-7 and MDA-MB-231) | |
Splicing regulation | LASTR [21] | Stress-induced lncRNA prevents the disassembly and recycling of spliceosome components and globally impairs splicing. | BC cell lines (MDA-MB-468, MDA-MB-231 and MCF10A) |
ZEB2-AS1 [22] | ZEB2-anti pairs with ZEB2 pre-mRNA, inhibiting the efficient splicing of the first exon of the protein-coding gene, promoting the retention of a first intron, which contains an internal ribosome entry site, favoring ZEB2 translation and therefore Ecadherin inhibition and the initiation of EMT. | Breast cancer cell lines MCF-7, BT-20, MDA-MB231 and MDB-MB435 | |
BC200 [23] | This lncRNA associates through RNA base pairing with the pre mRNA of Bcl-x, interfering with correct splicing and production of the Bcl-xS pro-apoptotic protein. | ER+ breast tumors, MCF-7 and TD47D cell lines | |
Organization of nuclear architecture | NEAT1 [24,25] | The structural and functional components of paraspecles, a nuclear compartment responsible for RNA processing. A high expression of NEAT1 in breast cancer is associated with increased therapy resistance and stemness. | Breast cancer primary samples and MDA-MB-231 |
MALAT1 [26] | MALAT1 is a component of nuclear speckles involved in the splicing of mRNAs. Its overexpression positively correlates with metastasis in breast cancer, however tumor-suppressive roles have been reported for this lncRNA. | Breast cancer primary samples and cell lines | |
XIST [27] | XIST is responsible for epigenetic silencing of the inactive X chromosome and its localization at the nuclear periphery. In breast cancer, XIST loss is associated with a dysregulated expression of the mediator complex and favors a less-differentiated, more tumorigenic phenotype. | Breast tumors primary samples, HME and HMLE cell lines | |
LncRNAs encoding polypeptides | RMRP [28] | Interacts with two RBPs (GRSF1 and HuR) in order to be localized into mitochondria and to regulate oxygen consumption | Hela and HEK293T |
LINC00908 [29] | Generates a small peptide of 60-aa (ASRPS) that binds STAT3, inhibiting its phosphorylation and affecting angiogenesis | BC cell lines | |
LINC00961 [30] | Generates a small peptide (SPAR) that interacts with lysosomal v-ATPase to negatively regulate mTORC1 activity | Murine muscle cells | |
LINC00665 [31] | Encodes for CIP2A-BP and competes with PP2A for the binding of CIP2A | BT549, MDA-MB-231 and Hs578T | |
EPR [32] | Encodes for an 8 kDa protein (EPRp) that localizes and stabilizes epithelial cell junctions | NMuMG and 4T1 | |
LINC00948 [33] | Generates a micropeptide (MLN) that inhibits SERCA, controlling Ca(2+) uptake into the sarcoplasmic reticulum. | Murine muscle cells | |
HOXB-AS3 [34] | Encodes a 53-aa peptide that binds hnRNP A1 that, in turn, regulates pyruvate kinase M splicing and glucose metabolism | Colon cancer cells | |
Sponges for miRNAs | Lnc-PNUTS [35] | Promotes EMT, migration, invasion in vitro and tumor growth and metastasis in vivo through ZEB1-2 upregulation by sponging miR-205. | HMLE, MCF7, MDA-MB-468, MCF10A and MDA-MB-231 |
LincROR [36,37] | Promotes EMT and stem-like state by sponging miR-205 and upregulating ZEB2. Favors BC cells survival in response to rapamycin by sponging miR-194-3p and thus upregulating MECP2. | MCF10A, MDA-MB-231 and MCF7 | |
H19 [38,39,40] | Acts as an miR-675 precursor and inhibits b- and c-Cbl. Competes with LIN28 for Let7a/b binding, derepressing all Let-7 targets, affecting stem cell self-renewal | BC cell lines | |
Lnc-ATB [41,42] | Promotes EMT, migration, invasion and tumor metastasis by sponging the miR-200 family and restoring EMT-TFs as Twist1 and ZEB1-2 | Hepatocellular carcinomas and MCF7 | |
TINCR [43] | Inhibits miR-199-5p transcription by recruiting DNMT1 at its locus. Moreover, TINCR acts as a sponge for miR-199-5p, promoting PD-L1 expression through USP20 stabilization. | BC cell lines | |
HOTTIP [44] | Sustains cancer stem-like properties by binding miR-148a-3p and increasing the Wnt signaling pathway | MCF7, T47D and MCF10A | |
Lnc-408 [45] | Promotes BC migration and invasion by acting as a sponge for miR-654-5p and upregulating its target LIMK1 | BC cell lines | |
TMEM105 [46] | Regulates Lactate Dehydrogenase A (LDHA) by sponging miR-1208 | MCF7, T47D, MDA-MB-231 and BT549 | |
Post-transcriptional regulation | PDCD4-AS1 [47] | Promotes the stability of PDCD4 mRNA through the formation of the RNA:RNA duplex | MCF10A derivatives (M1-M4) |
NKILA [15,48] | Binds to the NF-κB/IκB complex and inhibits IκB phosphorylation and NF-κB activation, thus blocking BC invasion, tumorigenesis and metastases. Modulates T-cell activation-induced cell death by interacting with the NF-kB/IkB complex, thus regulating the immunotherapy response in breast PDXs. | BC cell lines and BC PDXs | |
TINCR [49,50] | Supports mRNA stability thanks to the interaction with the STAU1 RNA-binding protein through 25-nt TINCR-box motifs. It is frequently dysregulated in different human cancer types. | Primary human keratinocytes and cancer cells | |
NORAD [51,52] | Acts as decoy of PUMILIO1/2 proteins through its binding at the PUMILIO responsive elements located in PUMILIO 3′ UTR, ultimately controlling genomic stability. In BC, it acts as a decoy of S100P, counteracting its pro-migratory, pro-invasive and pro-metastatic activity. | HCT116, BJ-5Ta cells and BC cell lines | |
IRENA [53] | Triggers NF-κB signaling in macrophages through PKR dimerization and increases the production of pro-inflammatory cytokines, ultimately fostering BC chemoresistance. | Breast primary samples, BC cell lines and conditional PyMT-IRENA KO mice | |
Lnc-PCIR [54] | Promotes tumorigenesis and metastasis through TAB3 and PABPC4 mRNA/protein up-regulation and TNF-α/NF-κB signaling pathway activation in TNBC. | TNBC cell lines | |
LINK-A [55] | Recruits BRK kinase to the EGFR:GPNMB complex, leading to BRK-dependent HIF1α phosphorylation and consequent normoxic HIF1α stabilization, thus promoting BC glycolysis reprogramming | Breast cancer primary samples and MDA-MB-231 | |
BDNF-AS [56] | Enhancer-transcribed lncRNAs promote tamoxifen resistance by scaffolding the TRIM21-mediated ubiquitination and subsequent degradation of the mTORC inhibitor RNH1. | BC primary samples and BC cell lines (MCF-7, MCF-7R and MDA-MB-231) | |
Organelles | SAMMSON [57,58] | Interacts with p32 and CARF to enhance mitochondrial metabolism and the synthesis of rRNAs | Melanoma |
GAS5 [59] | Negatively regulates MDH2 acetylation | HEK293T, MDA-MB-231 and MDA-MB-468 |
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Giuliani, B.; Tordonato, C.; Nicassio, F. Mechanisms of Long Non-Coding RNA in Breast Cancer. Int. J. Mol. Sci. 2023, 24, 4538. https://doi.org/10.3390/ijms24054538
Giuliani B, Tordonato C, Nicassio F. Mechanisms of Long Non-Coding RNA in Breast Cancer. International Journal of Molecular Sciences. 2023; 24(5):4538. https://doi.org/10.3390/ijms24054538
Chicago/Turabian StyleGiuliani, Bianca, Chiara Tordonato, and Francesco Nicassio. 2023. "Mechanisms of Long Non-Coding RNA in Breast Cancer" International Journal of Molecular Sciences 24, no. 5: 4538. https://doi.org/10.3390/ijms24054538