MA-induced LncRNA MALAT1 Aggravates Renal Fibrogenesis in Obstructive Nephropathy Through the MiR-145/FAK Pathway

Overview

Journal Aging (Albany NY)

Specialty Geriatrics

Date 2020 Mar 24

PMID 32203053

Citations 51

Authors

Peihua Liu

Bo Zhang

Zhi Chen

Yao He

Yongchao Du

Yuhang Liu

Xiang Chen

Affiliations

Soon will be listed here.

Abstract

Renal fibrosis is a key factor in chronic kidney disease (CKD). Long non-coding RNAs (lncRNAs) play important roles in the physiological and pathological progression of human diseases. However, the roles and underlying mechanisms of lncRNAs in renal fibrosis still need to be discovered. In this study, we first displayed the increased lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) expression in renal fibrosis in patients with obstructive nephropathy (ON). Then we found that transforming growth factor beta 1 (TGF-β1) induced epithelial-mesenchymal transition (EMT) and extracellular matrix (ECM) protein deposition, which promoted the viability, proliferation and migration of human renal proximal tubular epithelial (HK2) cells. Next, MALAT1/miR-145/focal adhesion kinase (FAK) pathway was confirmed to play an importment role in TGF-β1-induced renal fibrosis. In addition, the MALAT1/miR-145/FAK pathway was involved in the effect of dihydroartemisinin (DHA) on TGF-β1-induced renal fibrosis and . Furthermore, mA methyltransferase methyltransferase-like 3 (METTL3) was shown to be the main methyltransferase of mA modification on MALAT1.

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References

Li A, Peng R, Sun Y, Liu H, Peng H, Zhang Z . LincRNA 1700020I14Rik alleviates cell proliferation and fibrosis in diabetic nephropathy via miR-34a-5p/Sirt1/HIF-1α signaling. Cell Death Dis. 2018; 9(5):461. PMC: 5919933. DOI: 10.1038/s41419-018-0527-8. View

Yang Y, Hsu P, Chen Y, Yang Y . Dynamic transcriptomic mA decoration: writers, erasers, readers and functions in RNA metabolism. Cell Res. 2018; 28(6):616-624. PMC: 5993786. DOI: 10.1038/s41422-018-0040-8. View

Wang L, Yang F, Jia L, Yang A . Missing Links in Epithelial-Mesenchymal Transition: Long Non-Coding RNAs Enter the Arena. Cell Physiol Biochem. 2017; 44(4):1665-1680. DOI: 10.1159/000485766. View

Yang J, Liu Y . Dissection of key events in tubular epithelial to myofibroblast transition and its implications in renal interstitial fibrosis. Am J Pathol. 2001; 159(4):1465-75. PMC: 1850509. DOI: 10.1016/S0002-9440(10)62533-3. View

Jiang C, Li S, Li Y, Bai Y . Anticancer Effects of Dihydroartemisinin on Human Esophageal Cancer Cells In Vivo. Anal Cell Pathol (Amst). 2018; 2018:8759745. PMC: 5985077. DOI: 10.1155/2018/8759745. View

Wang J, Pan J, Li H, Long J, Fang F, Chen J . lncRNA ZEB1-AS1 Was Suppressed by p53 for Renal Fibrosis in Diabetic Nephropathy. Mol Ther Nucleic Acids. 2018; 12:741-750. PMC: 6095953. DOI: 10.1016/j.omtn.2018.07.012. View

KLAHR S . Obstructive nephropathy. Intern Med. 2000; 39(5):355-61. DOI: 10.2169/internalmedicine.39.355. View

Fogo A . Mechanisms of progression of chronic kidney disease. Pediatr Nephrol. 2007; 22(12):2011-22. PMC: 2064942. DOI: 10.1007/s00467-007-0524-0. View

Magistri M, Velmeshev D . Identification of Long Noncoding RNAs Associated to Human Disease Susceptibility. Methods Mol Biol. 2017; 1543:197-208. DOI: 10.1007/978-1-4939-6716-2_10. View

10.

Sun M, Gadad S, Kim D, Kraus W . Discovery, Annotation, and Functional Analysis of Long Noncoding RNAs Controlling Cell-Cycle Gene Expression and Proliferation in Breast Cancer Cells. Mol Cell. 2015; 59(4):698-711. PMC: 4546522. DOI: 10.1016/j.molcel.2015.06.023. View

11.

Zhang S . Mechanism of N-methyladenosine modification and its emerging role in cancer. Pharmacol Ther. 2018; 189:173-183. DOI: 10.1016/j.pharmthera.2018.04.011. View

12.

Wapinski O, Chang H . Long noncoding RNAs and human disease. Trends Cell Biol. 2011; 21(6):354-61. DOI: 10.1016/j.tcb.2011.04.001. View

13.

Bottinger E, Bitzer M . TGF-beta signaling in renal disease. J Am Soc Nephrol. 2002; 13(10):2600-10. DOI: 10.1097/01.asn.0000033611.79556.ae. View

14.

Meyer K, Jaffrey S . The dynamic epitranscriptome: N6-methyladenosine and gene expression control. Nat Rev Mol Cell Biol. 2014; 15(5):313-26. PMC: 4393108. DOI: 10.1038/nrm3785. View

15.

Mattick J . The genetic signatures of noncoding RNAs. PLoS Genet. 2009; 5(4):e1000459. PMC: 2667263. DOI: 10.1371/journal.pgen.1000459. View

16.

Bernard D, Prasanth K, Tripathi V, Colasse S, Nakamura T, Xuan Z . A long nuclear-retained non-coding RNA regulates synaptogenesis by modulating gene expression. EMBO J. 2010; 29(18):3082-93. PMC: 2944070. DOI: 10.1038/emboj.2010.199. View

17.

Shi H, Wei J, He C . Where, When, and How: Context-Dependent Functions of RNA Methylation Writers, Readers, and Erasers. Mol Cell. 2019; 74(4):640-650. PMC: 6527355. DOI: 10.1016/j.molcel.2019.04.025. View

18.

Meng X, Nikolic-Paterson D, Lan H . TGF-β: the master regulator of fibrosis. Nat Rev Nephrol. 2016; 12(6):325-38. DOI: 10.1038/nrneph.2016.48. View

19.

Zeisberg M, Kalluri R . The role of epithelial-to-mesenchymal transition in renal fibrosis. J Mol Med (Berl). 2004; 82(3):175-81. DOI: 10.1007/s00109-003-0517-9. View

20.

Latronico M, Condorelli G . Therapeutic applications of noncoding RNAs. Curr Opin Cardiol. 2015; 30(3):213-21. DOI: 10.1097/HCO.0000000000000162. View