The Role of miR‐497/EIF3A Axis in TGFβ1‐Induced Epithelial–Mesenchymal Transition and Extracellular Matrix in Rat Alveolar Epithelial Cells and Pulmonary Fibroblasts

Abstract

Multi-cause-induced interstitial lung disease, particularly pulmonary fibrosis, is a serious clinical concern. Fibroblasts have been suggested to have a major role, with it recently being revealed that some of these fibroblasts are derived from alveolar epithelial cells through epithelial-mesenchymal transition (EMT). Eukaryotic translation initiation factor 3 subunit A (EIF3A) is a protein that in humans is encoded by the EIF3A gene, and has been suggested to play roles in regulating translation of a subset of mRNAs and in regulating cell cycle progression and cell proliferation. In the present study, we chose a well-known TGFβ1-induced EMT model in alveolar epithelial cells to investigate the functional role of EIF3A. TGFβ1-induced EIF3A expression and EMT process in alveolar epithelial cells, after EIF3A knockdown, the EMT process could be partially reversed. Online tools and luciferase assays showed that miR-497 could inhibit EIF3A expression by directly binding to the 3'UTR of EIF3A. Ectopic miR-497 expression partially reversed TGFβ1-induced EMT in alveolar epithelial cells. In addition, miR-497 could suppress TGFβ1-induced pulmonary fibroblast proliferation and EIF3A, Collagen I and α-SMA protein levels. Taken together, EIF3A could promote TGFβ1-induced EMT in alveolar epithelial cells; miR-497 suppressed TGFβ1-induced EMT in alveolar epithelial cells TGFβ1-induced excessive proliferation and ECM in pulmonary fibroblast through inhibiting EIF3A by targeting. MiR-497/EIF3A axis shows the potential to be effective in the treatment of pulmonary fibrosis. J. Cell. Biochem. 118: 3401-3408, 2017. © 2017 Wiley Periodicals, Inc.

microRNA-186 in extracellular vesicles from bone marrow mesenchymal stem cells alleviates idiopathic pulmonary fibrosis via interaction with SOX4 and DKK1

“…Another miRNA, miR-26a, mediates the Lin28B/let-7d axis to exacerbate the epithelialmesenchymal transition in IPF [36]. Also, miR-497 has been showed to hinder the excessive proliferation of lung fibroblasts induced by TGFβ1 [37]. Consistent with our present findings, miR-186 can disrupt collagen V overexpression during IPF [13].…”

Novel insights into the interplay between m6A modification and noncoding RNAs in cancer

“…Hepatitis B X-interacting protein (HBXIP) inhibits let-7 g expression to upregulate IGF2BP2, thus leading to the formation of a positive feedback loop of HBXIP/let-7 g/IGF2BP2/HBXIP to accelerate cell proliferation in breast cancer [ 94 ]. miR-497 partially reverses transforming growth factor beta 1 (TGFβ1)-induced epithelial-mesenchymal transition (EMT) and pulmonary fibroblast proliferation through inhibiting eIF3a in alveolar epithelial cells [ 95 ].…”

Melatonin Attenuates Endothelial-to-Mesenchymal Transition of Glomerular Endothelial Cells via Regulating miR-497/ROCK in Diabetic Nephropathy

“…MiR-497 is a newly identified miRNA that inhibits epithelial-to-mesenchymal transition of cancer cells, keratinocytes, and alveolar epithelial cells [23,24,34]. A TargetScan analysis revealed that both ROCK1 and ROCK2 are potential targets of miR-497.…”

“…ROCK1 and ROCK2 reportedly have a post-transcriptional regulation mechanism [22], and miR-497 inhibits epithelial-to-mesenchymal transition [23,24]. Hence, we analyzed the relationship between miR-497 and ROCK1/ROCK2.…”