miR‐185 affected the EMT, cell viability, and proliferation via DNMT1/MEG3 pathway in TGF‐β1‐induced renal fibrosis

Abstract

Kidney fibrosis is usually the final manifestation of a wide variety of renal diseases. Recent years, research reported that lncRNAs played important roles in a variety of human diseases. However, the role and underlying mechanisms of lncRNAs in kidney fibrosis were complicated and largely unclear. In our study, we constructed the cell model of renal fibrosis in HK2 cells using TGF-β1 and found that lncRNA MEG3 was down-regulated in TGF-β1-induced renal fibrosis. We then found that overexpressed MEG3 inhibited the TGF-β1-induced promotion of EMT, cell viability and proliferation. Furthermore, we demonstrated that DNMT1 regulated the MEG3 expression via altering the CpGs methylation level of MEG3 promoter in TGF-β1-induced renal fibrosis. In addition, we further revealed that miR-185 could regulated the DNMT1 expression and thus, modulating the MEG3 in TGF-β1-induced renal fibrosis. Ultimately, our study illustrated that the modulation of the miR-185/ DNMT1/ MEG3 pathway exerted important roles in TGF-β1-induced renal fibrosis. In summary, our finding displayed a novel regulatory mechanism for TGF-β1-induced renal fibrosis, which provided a new potential therapeutic target for renal fibrosis.

LncRNA MEG3 mediates nickel oxide nanoparticles‐induced pulmonary fibrosis via suppressing TGF‐β1 expression and epithelial‐mesenchymal transition process

“…34 Likewise, the down-regulation of MEG3 was also described in TGF-β1-induced renal fibrosis, and the overexpressed MEG3 inhibited EMT in HK2 cells treated by TGF-β1. 36 On the contrary, Dong et al found that MEG3 siRNA silencing up-regulated the expression level of TGF-β1 in three different human hepatocellular carcinoma cell lines. 54 In this study, we found that lncRNA MEG3 was downregulated by NiO NPs both in rat lung tissues and A549 cells.…”

“…32 The lncRNA maternally expressed gene 3 (MEG3) expressed in most tissues and is demonstrated as a tumor suppressor. 33 Some evidences found that MEG3 was down-regulated in liver fibrosis, 34 cardiac fibrosis 35 and renal fibrosis, 36 which may be relate to TGF-β1 activation. Interestingly, a recent study found that MEG3 was up-regulated in idiopathic pulmonary fibrosis, 37 which was contrary to other organ fibrosis.…”

m6A-induced lncRNA MALAT1 aggravates renal fibrogenesis in obstructive nephropathy through the miR-145/FAK pathway

“…Advances in transcriptome analysis by RNA-seq technology have enabled the elucidation of lncRNA functions in renal fibrosis [50]. Several lncRNAs, such as MEG3, H19 and HOTAIR, were reported to play important roles in mediating TGFβ and renal fibrosis [45][46][47][48][49][50][51][52][53]. MALAT1 was reported to affect the cellular processes induced by TGF-β, such as EMT, ECM protein deposition, cell growth and cell mobility [43].…”

Emerging Roles of Long Non-Coding RNAs in Renal Fibrosis

“…Then researchers demonstrated that the over-expression of MEG3 significantly increased the expression of E-cadherin, and accordingly decreased N-cadherin and vimentin. Moreover, MEG3 up-regulation restrained cell viability and proliferation [ 95 ]. Furthermore, in HK-2 cells, studies showed that up-regulated lncRNA NEAT1 could lead to the over-expression of the α-SMA, vimentin, and the TGF-β1 and connective tissue growth factor (CTGF), and significantly promote apoptosis [ 96 ].…”

“…The overexpression of lncRNA MEG3 prevents TGF-β1-induced EMT, as shown by the elevated expression of E-cadherin and correspondingly inhibited protein level of N-cadherin and vimentin in HK2 transferred with overexpression plasmids of MEG3, and therefore, rescues TGF-β1-induced renal fibrosis. LncRNA MEG3 might, thus, function as a candidate therapeutic target in renal fibrotic processes, though further investigation is still required [ 95 ]. The expression of H19 was elevated in HK2 cells upon TGF-β2 simulation in vitro, an action which then promotes the phenotypic transition of EMT as shown by limited levels of E-cadherin, increased levels vimentin and α-SMA and ECM proteins.…”