Biofluid Specificity of Long Non-Coding RNA Profile in Hypertension: Relevance of Exosomal Fraction
Abstract
:1. Introduction
2. Results
2.1. Study Population
2.2. Non-Coding RNA Biotype Distribution According to Biofluid, Plasma, and Plasma Exosomes
2.3. Long Non-Coding RNA Biotype Overlapping between Biofluids
2.4. Functional Enrichment Analysis of the Differentially Expressed lncRNAs from Hypertensive Patients with Urinary Albumin Excretion
3. Discussion
4. Materials and Methods
4.1. Subjects and Samples
4.2. RNA Extraction, Small RNA Library Preparation, and Next-Generation Sequencing
4.3. Small RNA Sequencing Data Analysis
4.4. Statistical Analysis
4.5. Long Non-Coding RNA Target Predictions and Molecular Pathways Analyses
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Williams, B.; Mancia, G.; Spiering, W.; Agabiti Rosei, E.; Azizi, M.; Burnier, M.; Clement, D.L.; Coca, A.; De Simone, G.; Dominiczak, A.; et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH). J. Hypertens. 2018, 36, 1953–2041. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wu, G.; Jose, P.A.; Zeng, C. Noncoding RNAs in the Regulatory Network of Hypertension. Hypertension 2018, 72, 1047–1059. [Google Scholar] [CrossRef] [PubMed]
- 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] [PubMed] [Green Version]
- Asl, M.H.; Khelejani, F.P.; Mahdavi, S.Z.B.; Emrahi, L.; Jebelli, A.; Mokhtarzadeh, A. The various regulatory functions of long noncoding RNAs in apoptosis, cell cycle, and cellular senescence. J. Cell. Biochem. 2022. [Google Scholar] [CrossRef]
- Yao, R.-W.; Wang, Y.; Chen, L.-L. Cellular functions of long noncoding RNAs. Nat. Cell Biol. 2019, 21, 542–551. [Google Scholar] [CrossRef]
- Chen, S.; Chen, R.; Zhang, T.; Lin, S.; Chen, Z.; Zhao, B.; Li, H.; Wu, S. Relationship of cardiovascular disease risk factors and noncoding RNAs with hypertension: A case-control study. BMC Cardiovasc. Disord. 2018, 18, 58. [Google Scholar] [CrossRef] [Green Version]
- Matshazi, D.M.; Weale, C.J.; Erasmus, R.T.; Kengne, A.P.; Davids, S.F.G.; Raghubeer, S.; Davison, G.M.; Matsha, T.E. Circulating Levels of MicroRNAs Associated With Hypertension: A Cross-Sectional Study in Male and Female South African Participants. Front. Genet. 2021, 12, 710438. [Google Scholar] [CrossRef]
- Chen, K.; Ma, Y.; Wu, S.; Zhuang, Y.; Liu, X.; Lv, L.; Zhang, G. Construction and analysis of a lncRNA-miRNA-mRNA network based on competitive endogenous RNA reveals functional lncRNAs in diabetic cardiomyopathy. Mol. Med. Rep. 2019, 20, 1393–1403. [Google Scholar] [CrossRef]
- Zou, J.-B.; Chai, H.-B.; Zhang, X.-F.; Guo, D.-Y.; Tai, J.; Wang, Y.; Liang, Y.-L.; Wang, F.; Cheng, J.-X.; Wang, J.; et al. Reconstruction of the lncRNA-miRNA-mRNA network based on competitive endogenous RNA reveal functional lncRNAs in Cerebral Infarction. Sci. Rep. 2019, 9, 1–13. [Google Scholar] [CrossRef]
- Riffo-Campos, A.L.; Perez-Hernandez, J.; Ortega, A.; Martinez-Arroyo, O.; Flores-Chova, A.; Redon, J.; Cortes, R. Exosomal and Plasma Non-Coding RNA Signature Associated with Urinary Albumin Excretion in Hypertension. Int. J. Mol. Sci. 2022, 23, 823. [Google Scholar] [CrossRef]
- Elwazir, M.Y.; Hussein, M.H.; Toraih, E.A.; Al Ageeli, E.; Esmaeel, S.E.; Fawzy, M.S.; Faisal, S. Association of Angio-LncRNAs MIAT rs1061540/MALAT1 rs3200401 Molecular Variants with Gensini Score in Coronary Artery Disease Patients Undergoing Angiography. Biomolecules 2022, 12, 137. [Google Scholar] [CrossRef] [PubMed]
- Omura, J.; Habbout, K.; Shimauchi, T.; Wu, W.-H.; Breuils-Bonnet, S.; Tremblay, E.; Martineau, S.; Nadeau, V.; Gagnon, K.; Mazoyer, F.; et al. Identification of Long Noncoding RNA H19 as a New Biomarker and Therapeutic Target in Right Ventricular Failure in Pulmonary Arterial Hypertension. Circulation 2020, 142, 1464–1484. [Google Scholar] [CrossRef] [PubMed]
- Qin, S.; Predescu, D.; Carman, B.; Patel, P.; Chen, J.; Kim, M.; Lahm, T.; Geraci, M.; Predescu, S.A. Up-Regulation of the Long Noncoding RNA X-Inactive–Specific Transcript and the Sex Bias in Pulmonary Arterial Hypertension. Am. J. Pathol. 2021, 191, 1135–1150. [Google Scholar] [CrossRef] [PubMed]
- Zheng, D.; Hou, Y.; Li, Y.; Bian, Y.; Khan, M.; Li, F.; Huang, L.; Qiao, C. Long Non-coding RNA Gas5 Is Associated With Preeclampsia and Regulates Biological Behaviors of Trophoblast via MicroRNA-21. Front. Genet. 2020, 11, 188. [Google Scholar] [CrossRef]
- Jin, L.; Lin, X.; Yang, L.; Fan, X.; Wang, W.; Li, S.; Li, J.; Liu, X.; Bao, M.; Cui, X.; et al. AK098656, a Novel Vascular Smooth Muscle Cell–Dominant Long Noncoding RNA, Promotes Hypertension. Hypertension 2018, 71, 262–272. [Google Scholar] [CrossRef]
- Peng, W.; Cao, H.; Liu, K.; Guo, C.; Sun, Y.; Qi, H.; Liu, Z.; Xie, Y.; Liu, X.; Li, B.; et al. Identification of lncRNA-NR_104160 as a biomarker and construction of a lncRNA-related ceRNA network for essential hypertension. Am. J. Transl. Res. 2020, 12, 6060–6075. [Google Scholar]
- Yin, L.; Yao, J.; Deng, G.; Wang, X.; Cai, W.; Shen, J. Identification of candidate lncRNAs and circRNAs regulating WNT3/β-catenin signaling in essential hypertension. Aging 2020, 12, 8261–8288. [Google Scholar] [CrossRef]
- Martinez-Arroyo, O.; Ortega, A.; Redon, J.; Cortes, R. Therapeutic Potential of Extracellular Vesicles in Hypertension-Associated Kidney Disease. Hypertension 2021, 77, 28–38. [Google Scholar] [CrossRef]
- Tan, P.P.S.; Hall, D.; Chilian, W.M.; Chia, Y.C.; Zain, S.M.; Lim, H.M.; Kumar, D.N.; Ching, S.M.; Low, T.Y.; Noh, M.F.M.; et al. Exosomal microRNAs in the development of essential hypertension and its potential as biomarkers. Am. J. Physiol. Circ. Physiol. 2021, 320, H1486–H1497. [Google Scholar] [CrossRef]
- Li, Y.; Meng, Y.; Liu, Y.; Van Wijnen, A.J.; Eirin, A.; Lerman, L.O. Differentially Expressed Functional LncRNAs in Human Subjects With Metabolic Syndrome Reflect a Competing Endogenous RNA Network in Circulating Extracellular Vesicles. Front. Mol. Biosci. 2021, 8, 667056. [Google Scholar] [CrossRef]
- Perez-Hernandez, J.; Riffo-Campos, A.L.; Ortega, A.; Martinez-Arroyo, O.; Perez-Gil, D.; Olivares, D.; Solaz, E.; Martinez, F.; Martínez-Hervás, S.; Chaves, F.J.; et al. Urinary- and Plasma-Derived Exosomes Reveal a Distinct MicroRNA Signature Associated With Albuminuria in Hypertension. Hypertension 2021, 77, 960–971. [Google Scholar] [CrossRef] [PubMed]
- Michalik, K.M.; You, X.; Manavski, Y.; Doddaballapur, A.; Zörnig, M.; Braun, T.; John, D.; Ponomareva, Y.; Chen, W.; Uchida, S.; et al. Long Noncoding RNA MALAT1 Regulates Endothelial Cell Function and Vessel Growth. Circ. Res. 2014, 114, 1389–1397. [Google Scholar] [CrossRef] [PubMed]
- Wang, Y.-N.-Z.; Shan, K.; Yao, M.-D.; Yao, J.; Wang, J.-J.; Li, X.; Liu, B.; Zhang, Y.-Y.; Ji, Y.; Jiang, Q.; et al. Long Noncoding RNA-GAS5. Hypertension 2016, 68, 736–748. [Google Scholar] [CrossRef] [PubMed]
- Bell, R.D.; Long, X.; Lin, M.; Bergmann, J.H.; Nanda, V.; Cowan, S.L.; Zhou, Q.; Han, Y.; Spector, D.L.; Zheng, D.; et al. Identification and Initial Functional Characterization of a Human Vascular Cell–Enriched Long Noncoding RNA. Arter. Thromb. Vasc. Biol. 2014, 34, 1249–1259. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Villarroya-Beltri, C.; Gutierrez-Vazquez, C.; Sanchez-Cabo, F.; Pérez-Hernández, D.; Vázquez, J.; Martin-Cofreces, N.; Martinez-Herrera, D.J.; Pascual-Montano, A.; Mittelbrunn, M.; Sánchez-Madrid, F. Sumoylated hnRNPA2B1 controls the sorting of miRNAs into exosomes through binding to specific motifs. Nat. Commun. 2013, 4, 2980. [Google Scholar] [CrossRef] [Green Version]
- Vickers, K.C.; Palmisano, B.T.; Shoucri, B.M.; Shamburek, R.D.; Remaley, A.T. MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins. Nat. Cell Biol. 2011, 13, 423–433. [Google Scholar] [CrossRef] [Green Version]
- Yoon, J.-H.; Abdelmohsen, K.; Gorospe, M. Posttranscriptional Gene Regulation by Long Noncoding RNA. J. Mol. Biol. 2013, 425, 3723–3730. [Google Scholar] [CrossRef] [Green Version]
- Taverna, S.D.; Li, H.; Ruthenburg, A.; Allis, C.D.; Patel, D.J. How chromatin-binding modules interpret histone modifications: Lessons from professional pocket pickers. Nat. Struct. Mol. Biol. 2007, 14, 1025–1040. [Google Scholar] [CrossRef] [Green Version]
- Zhou, Z.; Li, X.; Liu, Z.; Huang, L.; Yao, Y.; Li, L.; Chen, J.; Zhang, R.; Zhou, J.; Wang, L.; et al. A Bromodomain-Containing Protein 4 (BRD4) Inhibitor Suppresses Angiogenesis by Regulating AP-1 Expression. Front. Pharmacol. 2020, 11, 1043. [Google Scholar] [CrossRef]
- Du, Y.; Topp, C.; Dawe, R.K. DNA Binding of Centromere Protein C (CENPC) Is Stabilized by Single-Stranded RNA. PLoS Genet. 2010, 6, e1000835. [Google Scholar] [CrossRef] [Green Version]
- Fang, Y.; Fullwood, M.J. Roles, Functions, and Mechanisms of Long Non-coding RNAs in Cancer. Genom. Proteom. Bioinform. 2016, 14, 42–54. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hsin, J.-P.; Manley, J.L. The RNA polymerase II CTD coordinates transcription and RNA processing. Genes Dev. 2012, 26, 2119–2137. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ribeiro, D.; Zanzoni, A.; Cipriano, A.; Ponti, R.D.; Spinelli, L.; Ballarino, M.; Bozzoni, I.; Tartaglia, G.G.; Brun, C. Protein complex scaffolding predicted as a prevalent function of long non-coding RNAs. Nucleic Acids Res. 2017, 46, 917–928. [Google Scholar] [CrossRef] [PubMed]
- Shiraishi-Yamaguchi, Y.; Furuichi, T. The Homer family proteins. Genome Biol. 2007, 8, 206. [Google Scholar] [CrossRef] [Green Version]
- Pelava, A.; Schneider, C.; Watkins, N.J. The importance of ribosome production, and the 5S RNP–MDM2 pathway, in health and disease. Biochem. Soc. Trans. 2016, 44, 1086–1090. [Google Scholar] [CrossRef] [Green Version]
- Saito, R.; Rocanin-Arjo, A.; You, Y.-H.; Darshi, M.; Van Espen, B.; Miyamoto, S.; Pham, J.; Pu, M.; Romoli, S.; Natarajan, L.; et al. Systems biology analysis reveals role of MDM2 in diabetic nephropathy. JCI Insight 2016, 1, e87877. [Google Scholar] [CrossRef] [Green Version]
- Wang, W.; Zhu, N.; Yan, T.; Shi, Y.-N.; Chen, J.; Zhang, C.-J.; Xie, X.-J.; Liao, D.-F.; Qin, L. The crosstalk: Exosomes and lipid metabolism. Cell Commun. Signal. 2020, 18, 1–12. [Google Scholar] [CrossRef]
- Grevengoed, T.J.; Klett, E.L.; Coleman, R.A. Acyl-CoA Metabolism and Partitioning. Annu. Rev. Nutr. 2014, 34, 1–30. [Google Scholar] [CrossRef] [Green Version]
- Kotani, A.; Ito, M.; Kudo, K. Non-coding RNAs and lipids mediate the function of extracellular vesicles in cancer cross-talk. Semin. Cancer Biol. 2021, 74, 121–133. [Google Scholar] [CrossRef]
- Klebanov, S.E.; Bochina, I.M.; Berman, A.L. A method for determining the classification of a protein in a given family at a low level of similarity. Zh. Evol. Biokhim. Fiziol. 1991, 27, 75–78. [Google Scholar]
- Dilmaghnai, N.A.; Shoorei, H.; Sharifi, G.; Mohaqiq, M.; Majidpoor, J.; Dinger, M.E.; Taheri, M.; Ghafouri-Fard, S. Non-coding RNAs modulate function of extracellular matrix proteins. Biomed. Pharmacother. 2021, 136, 111240. [Google Scholar] [CrossRef] [PubMed]
- D’Angelo, E.; Agostini, M. Long non-coding RNA and extracellular matrix: The hidden players in cancer-stroma cross-talk. Non-Coding RNA Res. 2018, 3, 174–177. [Google Scholar] [CrossRef] [PubMed]
- Qiu, Y.; Li, P.; Zhang, Z.; Wu, M. Insights Into Exosomal Non-Coding RNAs Sorting Mechanism and Clinical Application. Front. Oncol. 2021, 11, 664904. [Google Scholar] [CrossRef]
- Hu, H.; Ling, B.; Shi, Y.; Wu, H.; Zhu, B.; Meng, Y.; Zhang, G.-M. Plasma Exosome-Derived SENP1 May Be a Potential Prognostic Predictor for Melanoma. Front. Oncol. 2021, 11, 685009. [Google Scholar] [CrossRef] [PubMed]
- Mancia, G.; Fagard, R.; Narkiewicz, K.; Redon, J.; Zanchetti, A.; Böhm, M.; Christiaens, T.; Cífková, R.; De Backer, G.; Dominiczak, A.; et al. 2013 ESH/ESC Practice Guidelines for the Management of Arterial Hypertension. Blood Press. 2013, 23, 3–16. [Google Scholar] [CrossRef] [PubMed]
- Olivares, D.; Perez-Hernandez, J.; Perez-Gil, D.; Chaves, F.J.; Redon, J.; Cortes, R. Optimization of small RNA library preparation protocol from human urinary exosomes. J. Transl. Med. 2020, 18, 1–9. [Google Scholar] [CrossRef]
- Wingett, S.W.; Andrews, S. FastQ Screen: A tool for multi-genome mapping and quality control. F1000Research 2018, 7, 1338. [Google Scholar] [CrossRef]
- Dobin, A.; Davis, C.A.; Schlesinger, F.; Drenkow, J.; Zaleski, C.; Jha, S.; Batut, P.; Chaisson, M.; Gingeras, T.R. STAR: Ultrafast universal RNA-seq aligner. Bioinformatics 2013, 29, 15–21. [Google Scholar] [CrossRef]
- Li, H.; Handsaker, B.; Wysoker, A.; Fennell, T.; Ruan, J.; Homer, N.; Marth, G.; Abecasis, G.; Durbin, R. 1000 Genome Project Data Processing Subgroup. The Sequence Alignment/Map format and SAMtools. Bioinformatics 2009, 25, 2078–2079. [Google Scholar] [CrossRef] [Green Version]
- Frankish, A.; Diekhans, M.; Ferreira, A.-M.; Johnson, R.; Jungreis, I.; Loveland, J.; Mudge, J.M.; Sisu, C.; Wright, J.; Armstrong, J.; et al. GENCODE reference annotation for the human and mouse genomes. Nucleic Acids Res. 2019, 47, D766–D773. [Google Scholar] [CrossRef] [Green Version]
- Wang, J.; Zhang, P.; Lu, Y.; Li, Y.; Zheng, Y.; Kan, Y.; Chen, R.; He, S. piRBase: A comprehensive database of piRNA sequences. Nucleic Acids Res. 2018, 47, D175–D180. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Robinson, M.D.; McCarthy, D.J.; Smyth, G.K. EdgeR: A Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 2010, 26, 139–140. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fukunaga, T.; Iwakiri, J.; Ono, Y.; Hamada, M. LncRRIsearch: A Web Server for lncRNA-RNA Interaction Prediction Integrated With Tissue-Specific Expression and Subcellular Localization Data. Front. Genet. 2019, 10, 462. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Liao, Y.; Wang, J.; Jaehnig, E.J.; Shi, Z.; Zhang, B. WebGestalt 2019: Gene set analysis toolkit with revamped UIs and APIs. Nucleic Acids Res. 2019, 47, W199–W205. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Szklarczyk, D.; Gable, A.L.; Lyon, D.; Junge, A.; Wyder, S.; Huerta-Cepas, J.; Simonovic, M.; Doncheva, N.T.; Morris, J.H.; Bork, P.; et al. STRING v11: Protein–protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res. 2019, 47, D607–D613. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Shannon, P.; Markiel, A.; Ozier, O.; Baliga, N.S.; Wang, J.T.; Ramage, D.; Amin, N.; Schwikowski, B.; Ideker, T. Cytoscape: A software environment for integrated models of Biomolecular Interaction Networks. Genome Res. 2003, 13, 2498–2504. [Google Scholar] [CrossRef]
Variables | Albuminuria (UAE) (n = 22) | Normoalbuminuria (Non UAE) (n = 26) |
---|---|---|
Age (years) | 52.2 ± 8.3 | 55.0 ± 5.3 |
Gender (male) | 68.2% | 65.4% |
SBP (mmHg) | 136 ± 15 | 136 ± 24 |
DBP (mmHg) | 85 ± 10 | 87 ± 14 |
Glucose (mg/dL) | 122 ± 46 | 119 ± 41 |
Total Cholesterol (mg/dL) | 200 ± 34 ** | 173 ± 29 |
LDL (mg/dL) | 128 ± 30 ** | 108 ± 25 |
HDL (mg/dL) | 51 ± 14 | 50 ± 10 |
Triglycerides (mg/dL) | 153 ± 78 | 127 ± 60 |
Plasma creatinine (mg/dL) | 0.87 ± 0.30 | 0.90 ± 0.22 |
GFR (mL/min/1.73 m2) | 96 ± 27 | 87 ± 19 |
Body mass index (kg/m2) | 32 ± 7 | 30 ± 5 |
Obesity grade (%) Grade I Grade II Grade III | 29 9 14 | 20 12 8 |
Diabetes (%) | 41 | 35 |
Dyslipidemia (%) | 86 | 85 |
Smoking (%) | 55 | 48 |
UAE/Creatinine (mg/g) | 146.4 ± 144.3 *** | 3.1 ± 1.7 |
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Riffo-Campos, A.L.; Perez-Hernandez, J.; Martinez-Arroyo, O.; Ortega, A.; Flores-Chova, A.; Redon, J.; Cortes, R. Biofluid Specificity of Long Non-Coding RNA Profile in Hypertension: Relevance of Exosomal Fraction. Int. J. Mol. Sci. 2022, 23, 5199. https://doi.org/10.3390/ijms23095199
Riffo-Campos AL, Perez-Hernandez J, Martinez-Arroyo O, Ortega A, Flores-Chova A, Redon J, Cortes R. Biofluid Specificity of Long Non-Coding RNA Profile in Hypertension: Relevance of Exosomal Fraction. International Journal of Molecular Sciences. 2022; 23(9):5199. https://doi.org/10.3390/ijms23095199
Chicago/Turabian StyleRiffo-Campos, Angela L., Javier Perez-Hernandez, Olga Martinez-Arroyo, Ana Ortega, Ana Flores-Chova, Josep Redon, and Raquel Cortes. 2022. "Biofluid Specificity of Long Non-Coding RNA Profile in Hypertension: Relevance of Exosomal Fraction" International Journal of Molecular Sciences 23, no. 9: 5199. https://doi.org/10.3390/ijms23095199