Small Non-Coding RNA Profiling Identifies miR-181a-5p as a Mediator of Estrogen Receptor Beta-Induced Inhibition of Cholesterol Biosynthesis in Triple-Negative Breast Cancer
Abstract
:1. Introduction
2. Materials and Methods
2.1. Ethics Approval and Consent to Participate
2.2. TNBC Cell Line Maintenance and ERβ Clone Generation
2.3. The Cancer Genome Atlas (TCGA) Data Analysis
2.4. Immunohistochemistry Assay
2.5. Protein Extraction and Western Blotting
2.6. RNA Isolation and Quality Controls
2.7. sncRNA Sequencing and Data Analysis
3. Results
3.1. Characterization of Small Non-Coding RNA Expression Profile of Triple-Negative Breast Cancer Cell Lines
3.2. Association of ERβ mRNA Expression and Overall Survival of Breast Cancer Patients
3.3. ERβ Expression Induces a Profound Effect on Small Non-Coding RNA Profile in Triple-Negative Breast Cancer Cells
3.4. Upregulation of miR-181a-5p as an Auxiliary Mechanism of ERβ-Induced Cholesterol Biosynthesis Inhibition
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
- Guo, Y.; Yu, H.; Wang, J.; Sheng, Q.; Zhao, S.; Zhao, Y.Y.; Lehmann, B.D. The Landscape of Small Non-Coding RNAs in Triple-Negative Breast Cancer. Genes 2018, 9. [Google Scholar] [CrossRef] [Green Version]
- Aysola, K.; Desai, A.; Welch, C.; Xu, J.; Qin, Y.; Reddy, V.; Matthews, R.; Owens, C.; Okoli, J.; Beech, D.J.; et al. Triple Negative Breast Cancer—An Overview. Hered. Genet. 2013, 2013. [Google Scholar] [CrossRef]
- Foulkes, W.D.; Smith, I.E.; Reis-Filho, J.S. Triple-negative breast cancer. N. Engl. J. Med. 2010, 363, 1938–1948. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Andreopoulou, E.; Schweber, S.J.; Sparano, J.A.; McDaid, H.M. Therapies for triple negative breast cancer. Expert Opin. Pharmacother. 2015, 16, 983–998. [Google Scholar] [CrossRef] [PubMed]
- Boichuk, S.; Galembikova, A.; Sitenkov, A.; Khusnutdinov, R.; Dunaev, P.; Valeeva, E.; Usolova, N. Establishment and characterization of a triple negative basal-like breast cancer cell line with multi-drug resistance. Oncol. Lett. 2017, 14, 5039–5045. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Heldring, N.; Pike, A.; Andersson, S.; Matthews, J.; Cheng, G.; Hartman, J.; Tujague, M.; Ström, A.; Treuter, E.; Warner, M.; et al. Estrogen receptors: How do they signal and what are their targets. Physiol. Rev. 2007, 87, 905–931. [Google Scholar] [CrossRef] [Green Version]
- Tang, Z.R.; Zhang, R.; Lian, Z.X.; Deng, S.L.; Yu, K. Estrogen-Receptor Expression and Function in Female Reproductive Disease. Cells 2019, 8. [Google Scholar] [CrossRef] [Green Version]
- Thomas, C.; Gustafsson, J. The different roles of ER subtypes in cancer biology and therapy. Nat. Rev. Cancer 2011, 11, 597–608. [Google Scholar] [CrossRef]
- Huang, B.; Omoto, Y.; Iwase, H.; Yamashita, H.; Toyama, T.; Coombes, R.C.; Filipovic, A.; Warner, M.; Gustafsson, J. Differential expression of estrogen receptor α, β1, and β2 in lobular and ductal breast cancer. Proc. Natl. Acad. Sci. USA 2014, 111, 1933–1938. [Google Scholar] [CrossRef] [Green Version]
- Moore, J.T.; McKee, D.D.; Slentz-Kesler, K.; Moore, L.B.; Jones, S.A.; Horne, E.L.; Su, J.L.; Kliewer, S.A.; Lehmann, J.M.; Willson, T.M. Cloning and characterization of human estrogen receptor beta isoforms. Biochem. Biophys. Res. Commun. 1998, 247, 75–78. [Google Scholar] [CrossRef]
- Nelson, A.W.; Groen, A.J.; Miller, J.L.; Warren, A.Y.; Holmes, K.A.; Tarulli, G.A.; Tilley, W.D.; Katzenellenbogen, B.S.; Hawse, J.R.; Gnanapragasam, V.J.; et al. Comprehensive assessment of estrogen receptor beta antibodies in cancer cell line models and tissue reveals critical limitations in reagent specificity. Mol. Cell. Endocrinol. 2017, 440, 138–150. [Google Scholar] [CrossRef] [Green Version]
- Andersson, S.; Sundberg, M.; Pristovsek, N.; Ibrahim, A.; Jonsson, P.; Katona, B.; Clausson, C.M.; Zieba, A.; Ramström, M.; Söderberg, O.; et al. Insufficient antibody validation challenges oestrogen receptor beta research. Nat. Commun. 2017, 8, 15840. [Google Scholar] [CrossRef] [PubMed]
- Yan, Y.; Li, X.; Blanchard, A.; Bramwell, V.H.; Pritchard, K.I.; Tu, D.; Shepherd, L.; Myal, Y.; Penner, C.; Watson, P.H.; et al. Expression of both estrogen receptor-beta 1 (ER-β1) and its co-regulator steroid receptor RNA activator protein (SRAP) are predictive for benefit from tamoxifen therapy in patients with estrogen receptor-alpha (ER-α)-negative early breast cancer (EBC). Ann. Oncol. 2013, 24, 1986–1993. [Google Scholar] [CrossRef] [PubMed]
- Smart, E.; Hughes, T.; Smith, L.; Speirs, V. Estrogen receptor β: Putting a positive into triple negative breast cancer? Horm. Mol. Biol. Clin. Investig. 2013, 16, 117–123. [Google Scholar] [CrossRef] [PubMed]
- Alexandrova, E.; Giurato, G.; Saggese, P.; Pecoraro, G.; Lamberti, J.; Ravo, M.; Rizzo, F.; Rocco, D.; Tarallo, R.; Nyman, T.A.; et al. Interaction Proteomics Identifies ERbeta Association with Chromatin Repressive Complexes to Inhibit Cholesterol Biosynthesis and Exert An Oncosuppressive Role in Triple-negative Breast Cancer. Mol. Cell. Proteom. 2020, 19, 245–260. [Google Scholar] [CrossRef]
- Romano, G.; Veneziano, D.; Acunzo, M.; Croce, C.M. Small non-coding RNA and cancer. Carcinogenesis 2017, 38, 485–491. [Google Scholar] [CrossRef] [Green Version]
- Bartel, D.P. MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell 2004, 116, 281–297. [Google Scholar] [CrossRef] [Green Version]
- Ventura, A.; Jacks, T. MicroRNAs and cancer: Short RNAs go a long way. Cell 2009, 136, 586–591. [Google Scholar] [CrossRef] [Green Version]
- Macfarlane, L.A.; Murphy, P.R. MicroRNA: Biogenesis, Function and Role in Cancer. Curr. Genom. 2010, 11, 537–561. [Google Scholar] [CrossRef] [Green Version]
- Condrat, C.E.; Thompson, D.C.; Barbu, M.G.; Bugnar, O.L.; Boboc, A.; Cretoiu, D.; Suciu, N.; Cretoiu, S.M.; Voinea, S.C. miRNAs as Biomarkers in Disease: Latest Findings Regarding Their Role in Diagnosis and Prognosis. Cells 2020, 9. [Google Scholar] [CrossRef] [Green Version]
- Moloney, B.M.; Gilligan, K.E.; Joyce, D.P.; O’Neill, C.P.; O’Brien, K.P.; Khan, S.; Glynn, C.L.; Waldron, R.M.; Maguire, C.M.; Holian, E.; et al. Investigating the Potential and Pitfalls of EV-Encapsulated MicroRNAs as Circulating Biomarkers of Breast Cancer. Cells 2020, 9. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Grober, O.M.; Mutarelli, M.; Giurato, G.; Ravo, M.; Cicatiello, L.; De Filippo, M.R.; Ferraro, L.; Nassa, G.; Papa, M.F.; Paris, O.; et al. Global analysis of estrogen receptor beta binding to breast cancer cell genome reveals an extensive interplay with estrogen receptor alpha for target gene regulation. BMC Genom. 2011, 12, 36. [Google Scholar] [CrossRef]
- Paris, O.; Ferraro, L.; Grober, O.M.; Ravo, M.; De Filippo, M.R.; Giurato, G.; Nassa, G.; Tarallo, R.; Cantarella, C.; Rizzo, F.; et al. Direct regulation of microRNA biogenesis and expression by estrogen receptor beta in hormone-responsive breast cancer. Oncogene 2012, 31, 4196–4206. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tarallo, R.; Giurato, G.; Bruno, G.; Ravo, M.; Rizzo, F.; Salvati, A.; Ricciardi, L.; Marchese, G.; Cordella, A.; Rocco, T.; et al. The nuclear receptor ERβ engages AGO2 in regulation of gene transcription, RNA splicing and RISC loading. Genome Biol. 2017, 18, 189. [Google Scholar] [CrossRef] [PubMed]
- Network, C.G.A. Comprehensive molecular portraits of human breast tumours. Nature 2012, 490, 61–70. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Alexandrova, E.; Miglino, N.; Hashim, A.; Nassa, G.; Stellato, C.; Tamm, M.; Baty, F.; Brutsche, M.; Weisz, A.; Borger, P. Small RNA profiling reveals deregulated phosphatase and tensin homolog (PTEN)/phosphoinositide 3-kinase (PI3K)/Akt pathway in bronchial smooth muscle cells from asthmatic patients. J. Allergy Clin. Immunol. 2016, 137, 58–67. [Google Scholar] [CrossRef] [Green Version]
- Panero, R.; Rinaldi, A.; Memoli, D.; Nassa, G.; Ravo, M.; Rizzo, F.; Tarallo, R.; Milanesi, L.; Weisz, A.; Giurato, G. iSmaRT: A toolkit for a comprehensive analysis of small RNA-Seq data. Bioinformatics 2017, 33, 938–940. [Google Scholar] [CrossRef] [Green Version]
- Kuksa, P.P.; Amlie-Wolf, A.; Katanic, Ž.; Valladares, O.; Wang, L.S.; Leung, Y.Y. SPAR: Small RNA-seq portal for analysis of sequencing experiments. Nucleic Acids Res. 2018, 46, W36–W42. [Google Scholar] [CrossRef]
- Kozomara, A.; Birgaoanu, M.; Griffiths-Jones, S. miRBase: From microRNA sequences to function. Nucleic Acids Res. 2019, 47, D155–D162. [Google Scholar] [CrossRef]
- Sai Lakshmi, S.; Agrawal, S. piRNABank: A web resource on classified and clustered Piwi-interacting RNAs. Nucleic Acids Res. 2008, 36, D173–D177. [Google Scholar] [CrossRef]
- Fujita, P.A.; Rhead, B.; Zweig, A.S.; Hinrichs, A.S.; Karolchik, D.; Cline, M.S.; Goldman, M.; Barber, G.P.; Clawson, H.; Coelho, A.; et al. The UCSC Genome Browser database: Update 2011. Nucleic Acids Res. 2011, 39, D876–D882. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kalvari, I.; Argasinska, J.; Quinones-Olvera, N.; Nawrocki, E.P.; Rivas, E.; Eddy, S.R.; Bateman, A.; Finn, R.D.; Petrov, A.I. Rfam 13.0: Shifting to a genome-centric resource for non-coding RNA families. Nucleic Acids Res. 2018, 46, D335–D342. [Google Scholar] [CrossRef] [PubMed]
- Pruitt, K.D.; Tatusova, T.; Klimke, W.; Maglott, D.R. NCBI Reference Sequences: Current status, policy and new initiatives. Nucleic Acids Res. 2009, 37, D32–D36. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kuksa, P.P.; Amlie-Wolf, A.; Katanić, Ž.; Valladares, O.; Wang, L.S.; Leung, Y.Y. DASHR 2.0: Integrated database of human small non-coding RNA genes and mature products. Bioinformatics 2019, 35, 1033–1039. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Love, M.I.; Huber, W.; Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014, 15, 550. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sticht, C.; De La Torre, C.; Parveen, A.; Gretz, N. miRWalk: An online resource for prediction of microRNA binding sites. PLoS ONE 2018, 13, e0206239. [Google Scholar] [CrossRef]
- Saeed, A.I.; Sharov, V.; White, J.; Li, J.; Liang, W.; Bhagabati, N.; Braisted, J.; Klapa, M.; Currier, T.; Thiagarajan, M.; et al. TM4: A free, open-source system for microarray data management and analysis. Biotechniques 2003, 34, 374–378. [Google Scholar] [CrossRef] [Green Version]
- Gentleman, R.C.; Carey, V.J.; Bates, D.M.; Bolstad, B.; Dettling, M.; Dudoit, S.; Ellis, B.; Gautier, L.; Ge, Y.; Gentry, J.; et al. Bioconductor: Open software development for computational biology and bioinformatics. Genome Biol. 2004, 5, R80. [Google Scholar] [CrossRef] [Green Version]
- Bisso, A.; Faleschini, M.; Zampa, F.; Capaci, V.; De Santa, J.; Santarpia, L.; Piazza, S.; Cappelletti, V.; Daidone, M.; Agami, R.; et al. Oncogenic miR-181a/b affect the DNA damage response in aggressive breast cancer. Cell Cycle 2013, 12, 1679–1687. [Google Scholar] [CrossRef]
- Radojicic, J.; Zaravinos, A.; Vrekoussis, T.; Kafousi, M.; Spandidos, D.A.; Stathopoulos, E.N. MicroRNA expression analysis in triple-negative (ER, PR and Her2/neu) breast cancer. Cell Cycle 2011, 10, 507–517. [Google Scholar] [CrossRef] [Green Version]
- Gasparini, P.; Cascione, L.; Fassan, M.; Lovat, F.; Guler, G.; Balci, S.; Irkkan, C.; Morrison, C.; Croce, C.M.; Shapiro, C.L.; et al. microRNA expression profiling identifies a four microRNA signature as a novel diagnostic and prognostic biomarker in triple negative breast cancers. Oncotarget 2014, 5, 1174–1184. [Google Scholar] [CrossRef] [PubMed]
- Tang, W.; Zhu, J.; Su, S.; Wu, W.; Liu, Q.; Su, F.; Yu, F. MiR-27 as a prognostic marker for breast cancer progression and patient survival. PLoS ONE 2012, 7, e51702. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ren, Y.Q.; Fu, F.; Han, J. MiR-27a modulates radiosensitivity of triple-negative breast cancer (TNBC) cells by targeting CDC27. Med. Sci. Monit. 2015, 21, 1297–1303. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yan, L.X.; Wu, Q.N.; Zhang, Y.; Li, Y.Y.; Liao, D.Z.; Hou, J.H.; Fu, J.; Zeng, M.S.; Yun, J.P.; Wu, Q.L.; et al. Knockdown of miR-21 in human breast cancer cell lines inhibits proliferation, in vitro migration and in vivo tumor growth. Breast Cancer Res. 2011, 13, R2. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bai, X.; Han, G.; Liu, Y.; Jiang, H.; He, Q. MiRNA-20a-5p promotes the growth of triple-negative breast cancer cells through targeting RUNX3. Biomed. Pharmacother. 2018, 103, 1482–1489. [Google Scholar] [CrossRef] [PubMed]
- Xiong, B.; Lei, X.; Zhang, L.; Fu, J. miR-103 regulates triple negative breast cancer cells migration and invasion through targeting olfactomedin 4. Biomed. Pharmacother. 2017, 89, 1401–1408. [Google Scholar] [CrossRef]
- Chen, H.; Pan, H.; Qian, Y.; Zhou, W.; Liu, X. MiR-25-3p promotes the proliferation of triple negative breast cancer by targeting BTG2. Mol. Cancer 2018, 17, 4. [Google Scholar] [CrossRef]
- Jang, M.H.; Kim, H.J.; Gwak, J.M.; Chung, Y.R.; Park, S.Y. Prognostic value of microRNA-9 and microRNA-155 expression in triple-negative breast cancer. Hum. Pathol. 2017, 68, 69–78. [Google Scholar] [CrossRef]
- Zhou, M.; Liu, Z.; Zhao, Y.; Ding, Y.; Liu, H.; Xi, Y.; Xiong, W.; Li, G.; Lu, J.; Fodstad, O.; et al. MicroRNA-125b confers the resistance of breast cancer cells to paclitaxel through suppression of pro-apoptotic Bcl-2 antagonist killer 1 (Bak1) expression. J. Biol. Chem. 2010, 285, 21496–21507. [Google Scholar] [CrossRef] [Green Version]
- Crippa, E.; Lusa, L.; De Cecco, L.; Marchesi, E.; Calin, G.A.; Radice, P.; Manoukian, S.; Peissel, B.; Daidone, M.G.; Gariboldi, M.; et al. miR-342 regulates BRCA1 expression through modulation of ID4 in breast cancer. PLoS ONE 2014, 9, e87039. [Google Scholar] [CrossRef]
- Liu, X.; Tang, H.; Chen, J.; Song, C.; Yang, L.; Liu, P.; Wang, N.; Xie, X.; Lin, X. MicroRNA-101 inhibits cell progression and increases paclitaxel sensitivity by suppressing MCL-1 expression in human triple-negative breast cancer. Oncotarget 2015, 6, 20070–20083. [Google Scholar] [CrossRef] [PubMed]
- Liu, P.; Ye, F.; Xie, X.; Li, X.; Tang, H.; Li, S.; Huang, X.; Song, C.; Wei, W. mir-101-3p is a key regulator of tumor metabolism in triple negative breast cancer targeting AMPK. Oncotarget 2016, 7, 35188–35198. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Li, J.; Lai, Y.; Ma, J.; Liu, Y.; Bi, J.; Zhang, L.; Chen, L.; Yao, C.; Lv, W.; Chang, G.; et al. miR-17-5p suppresses cell proliferation and invasion by targeting ETV1 in triple-negative breast cancer. BMC Cancer 2017, 17, 745. [Google Scholar] [CrossRef] [PubMed]
- Shyamasundar, S.; Lim, J.P.; Bay, B.H. miR-93 inhibits the invasive potential of triple-negative breast cancer cells in vitro via protein kinase WNK1. Int. J. Oncol. 2016, 49, 2629–2636. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Shi, Z.; Li, Y.; Qian, X.; Hu, Y.; Liu, J.; Zhang, S.; Zhang, J. MiR-340 Inhibits Triple-Negative Breast Cancer Progression by Reversing EZH2 Mediated miRNAs Dysregulated Expressions. J. Cancer 2017, 8, 3037–3048. [Google Scholar] [CrossRef] [PubMed]
- Luo, L.J.; Yang, F.; Ding, J.J.; Yan, D.L.; Wang, D.D.; Yang, S.J.; Ding, L.; Li, J.; Chen, D.; Ma, R.; et al. MiR-31 inhibits migration and invasion by targeting SATB2 in triple negative breast cancer. Gene 2016, 594, 47–58. [Google Scholar] [CrossRef]
- Sossey-Alaoui, K.; Downs-Kelly, E.; Das, M.; Izem, L.; Tubbs, R.; Plow, E.F. WAVE3, an actin remodeling protein, is regulated by the metastasis suppressor microRNA, miR-31, during the invasion-metastasis cascade. Int. J. Cancer 2011, 129, 1331–1343. [Google Scholar] [CrossRef] [Green Version]
- Körner, C.; Keklikoglou, I.; Bender, C.; Wörner, A.; Münstermann, E.; Wiemann, S. MicroRNA-31 sensitizes human breast cells to apoptosis by direct targeting of protein kinase C epsilon (PKCepsilon). J. Biol. Chem. 2013, 288, 8750–8761. [Google Scholar] [CrossRef] [Green Version]
- Baldassari, F.; Zerbinati, C.; Galasso, M.; Corrà, F.; Minotti, L.; Agnoletto, C.; Previati, M.; Croce, C.M.; Volinia, S. Screen for MicroRNA and Drug Interactions in Breast Cancer Cell Lines Points to miR-126 as a Modulator of CDK4/6 and PIK3CA Inhibitors. Front. Genet. 2018, 9, 174. [Google Scholar] [CrossRef]
- El Majzoub, R.; Fayyad-Kazan, M.; Nasr El Dine, A.; Makki, R.; Hamade, E.; Grée, R.; Hachem, A.; Talhouk, R.; Fayyad-Kazan, H.; Badran, B. A thiosemicarbazone derivative induces triple negative breast cancer cell apoptosis: Possible role of miRNA-125a-5p and miRNA-181a-5p. Genes Genom. 2019, 41, 1431–1443. [Google Scholar] [CrossRef]
- Ouyang, M.; Li, Y.; Ye, S.; Ma, J.; Lu, L.; Lv, W.; Chang, G.; Li, X.; Li, Q.; Wang, S.; et al. MicroRNA profiling implies new markers of chemoresistance of triple-negative breast cancer. PLoS ONE 2014, 9, e96228. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Niu, J.; Xue, A.; Chi, Y.; Xue, J.; Wang, W.; Zhao, Z.; Fan, M.; Yang, C.H.; Shao, Z.M.; Pfeffer, L.M.; et al. Induction of miRNA-181a by genotoxic treatments promotes chemotherapeutic resistance and metastasis in breast cancer. Oncogene 2016, 35, 1302–1313. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Taylor, M.A.; Sossey-Alaoui, K.; Thompson, C.L.; Danielpour, D.; Schiemann, W.P. TGF-β upregulates miR-181a expression to promote breast cancer metastasis. J. Clin. Invest. 2013, 123, 150–163. [Google Scholar] [CrossRef] [Green Version]
- Liu, H.; Wang, Y.; Li, X.; Zhang, Y.J.; Li, J.; Zheng, Y.Q.; Liu, M.; Song, X.; Li, X.R. Expression and regulatory function of miRNA-182 in triple-negative breast cancer cells through its targeting of profilin 1. Tumour Biol. 2013, 34, 1713–1722. [Google Scholar] [CrossRef] [PubMed]
- Moskwa, P.; Buffa, F.M.; Pan, Y.; Panchakshari, R.; Gottipati, P.; Muschel, R.J.; Beech, J.; Kulshrestha, R.; Abdelmohsen, K.; Weinstock, D.M.; et al. miR-182-mediated downregulation of BRCA1 impacts DNA repair and sensitivity to PARP inhibitors. Mol. Cell 2011, 41, 210–220. [Google Scholar] [CrossRef] [PubMed]
- M’hamed, I.F.; Privat, M.; Trimeche, M.; Penault-Llorca, F.; Bignon, Y.J.; Kenani, A. miR-10b, miR-26a, miR-146a And miR-153 Expression in Triple Negative Vs Non Triple Negative Breast Cancer: Potential Biomarkers. Pathol. Oncol. Res. 2017, 23, 815–827. [Google Scholar] [CrossRef]
- Liu, P.; Tang, H.; Chen, B.; He, Z.; Deng, M.; Wu, M.; Liu, X.; Yang, L.; Ye, F.; Xie, X. miR-26a suppresses tumour proliferation and metastasis by targeting metadherin in triple negative breast cancer. Cancer Lett. 2015, 357, 384–392. [Google Scholar] [CrossRef]
- Gao, J.; Li, L.; Wu, M.; Liu, M.; Xie, X.; Guo, J.; Tang, H. MiR-26a inhibits proliferation and migration of breast cancer through repression of MCL-1. PLoS ONE 2013, 8, e65138. [Google Scholar] [CrossRef]
- Nassa, G.; Tarallo, R.; Giurato, G.; De Filippo, M.R.; Ravo, M.; Rizzo, F.; Stellato, C.; Ambrosino, C.; Baumann, M.; Lietzèn, N.; et al. Post-transcriptional regulation of human breast cancer cell proteome by unliganded estrogen receptor β via microRNAs. Mol. Cell. Proteom. 2014, 13, 1076–1090. [Google Scholar] [CrossRef] [Green Version]
- Al-Nakhle, H.; Burns, P.A.; Cummings, M.; Hanby, A.M.; Hughes, T.A.; Satheesha, S.; Shaaban, A.M.; Smith, L.; Speirs, V. Estrogen receptor {beta}1 expression is regulated by miR-92 in breast cancer. Cancer Res. 2010, 70, 4778–4784. [Google Scholar] [CrossRef] [Green Version]
- Yang, C.; Tabatabaei, S.N.; Ruan, X.; Hardy, P. The Dual Regulatory Role of MiR-181a in Breast Cancer. Cell. Physiol. Biochem. 2017, 44, 843–856. [Google Scholar] [CrossRef] [PubMed]
- Ding, L.; Gu, H.; Xiong, X.; Ao, H.; Cao, J.; Lin, W.; Yu, M.; Lin, J.; Cui, Q. MicroRNAs Involved in Carcinogenesis, Prognosis, Therapeutic Resistance and Applications in Human Triple-Negative Breast Cancer. Cells 2019, 8. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Liu, S.; Wang, Z.; Liu, Z.; Shi, S.; Zhang, Z.; Zhang, J.; Lin, H. miR-221/222 activate the Wnt/β-catenin signaling to promote triple-negative breast cancer. J. Mol. Cell Biol. 2018, 10, 302–315. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zheng, Y.; Lv, X.; Wang, X.; Wang, B.; Shao, X.; Huang, Y.; Shi, L.; Chen, Z.; Huang, J.; Huang, P. MiR-181b promotes chemoresistance in breast cancer by regulating Bim expression. Oncol. Rep. 2016, 35, 683–690. [Google Scholar] [CrossRef] [Green Version]
- Wu, J.; Sun, Z.; Sun, H.; Li, Y. MicroRNA-27a promotes tumorigenesis via targeting AKT in triple negative breast cancer. Mol. Med. Rep. 2018, 17, 562–570. [Google Scholar] [CrossRef] [Green Version]
- Hawse, J.R.; Carter, J.M.; Aspros, K.G.M.; Bruinsma, E.S.; Koepplin, J.W.; Negron, V.; Subramaniam, M.; Ingle, J.N.; Rech, K.L.; Goetz, M.P. Optimized immunohistochemical detection of estrogen receptor beta using two validated monoclonal antibodies confirms its expression in normal and malignant breast tissues. Breast Cancer Res. Treat. 2019. [Google Scholar] [CrossRef]
- Ehmsen, S.; Pedersen, M.H.; Wang, G.; Terp, M.G.; Arslanagic, A.; Hood, B.L.; Conrads, T.P.; Leth-Larsen, R.; Ditzel, H.J. Increased Cholesterol Biosynthesis Is a Key Characteristic of Breast Cancer Stem Cells Influencing Patient Outcome. Cell Rep. 2019, 27, 3927–3938. [Google Scholar] [CrossRef] [Green Version]
- Cai, D.; Wang, J.; Gao, B.; Li, J.; Wu, F.; Zou, J.X.; Xu, J.; Jiang, Y.; Zou, H.; Huang, Z.; et al. RORγ is a targetable master regulator of cholesterol biosynthesis in a cancer subtype. Nat. Commun. 2019, 10, 4621. [Google Scholar] [CrossRef]
- Berber, U.; Yilmaz, I.; Narli, G.; Haholu, A.; Kucukodaci, Z.; Demirel, D. miR-205 and miR-200c: Predictive Micro RNAs for Lymph Node Metastasis in Triple Negative Breast Cancer. J. Breast Cancer 2014, 17, 143–148. [Google Scholar] [CrossRef] [Green Version]
- Wang, B.; Li, J.; Sun, M.; Sun, L.; Zhang, X. miRNA expression in breast cancer varies with lymph node metastasis and other clinicopathologic features. IUBMB Life 2014, 66, 371–377. [Google Scholar] [CrossRef]
- Li, Y.; Kuscu, C.; Banach, A.; Zhang, Q.; Pulkoski-Gross, A.; Kim, D.; Liu, J.; Roth, E.; Li, E.; Shroyer, K.R.; et al. miR-181a-5p Inhibits Cancer Cell Migration and Angiogenesis via Downregulation of Matrix Metalloproteinase-14. Cancer Res. 2015, 75, 2674–2685. [Google Scholar] [CrossRef] [PubMed] [Green Version]
Characteristics | ERβ+ | ERβ− |
---|---|---|
Number | 12 (27%) | 32 (73%) |
Age (Years) | ||
Median (range) | 62 (27–77) | 62 (24–91) |
Stage (FIGO) | ||
I–II | 0 | 4 (12%) |
III–IV | 12 (100%) | 28 (88%) |
Histotype | ||
IDC | 9 (75%) | 23 (72%) |
IDLC | 1 (8%) | 0 |
ILC | 2 (17%) | 3 (9%) |
AC | 0 | 2 (6%) |
Others | 0 | 4 (13%) |
Histological Grade | ||
G1 | 7 (58%) | 15 (47%) |
G2 | 5 (42%) | 13 (41%) |
G3 | 0 | 3 (9%) |
NA | 0 | 1 (3%) |
Disease Progression | ||
No progression | 3 (25%) | 16 (50%) |
Progression | 7 (58%) | 5 (16%) |
NA | 2 (17%) | 11 (34%) |
Lymph Node Metastasis | ||
Negative | 7 (58%) | 17 (53%) |
Positive | 5 (42%) | 15 (47%) |
Ki67 | ||
<20% | 0 | 7 (22%) |
>20% | 12 (100%) | 24 (75%) |
ND | 0 | 1 (3%) |
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Alexandrova, E.; Lamberti, J.; Saggese, P.; Pecoraro, G.; Memoli, D.; Mirici Cappa, V.; Ravo, M.; Iorio, R.; Tarallo, R.; Rizzo, F.; et al. Small Non-Coding RNA Profiling Identifies miR-181a-5p as a Mediator of Estrogen Receptor Beta-Induced Inhibition of Cholesterol Biosynthesis in Triple-Negative Breast Cancer. Cells 2020, 9, 874. https://doi.org/10.3390/cells9040874
Alexandrova E, Lamberti J, Saggese P, Pecoraro G, Memoli D, Mirici Cappa V, Ravo M, Iorio R, Tarallo R, Rizzo F, et al. Small Non-Coding RNA Profiling Identifies miR-181a-5p as a Mediator of Estrogen Receptor Beta-Induced Inhibition of Cholesterol Biosynthesis in Triple-Negative Breast Cancer. Cells. 2020; 9(4):874. https://doi.org/10.3390/cells9040874
Chicago/Turabian StyleAlexandrova, Elena, Jessica Lamberti, Pasquale Saggese, Giovanni Pecoraro, Domenico Memoli, Valeria Mirici Cappa, Maria Ravo, Roberta Iorio, Roberta Tarallo, Francesca Rizzo, and et al. 2020. "Small Non-Coding RNA Profiling Identifies miR-181a-5p as a Mediator of Estrogen Receptor Beta-Induced Inhibition of Cholesterol Biosynthesis in Triple-Negative Breast Cancer" Cells 9, no. 4: 874. https://doi.org/10.3390/cells9040874