miR-26a suppresses EMT by disrupting the Lin28B/let-7d axis: potential cross-talks among miRNAs in IPF

Haihai Liang, Shanshan Liu, Yang Chen, Xue Bai, Li Liu, Yuechao Dong, Meiyu Hu, Xiaomin Su, Yingzhun Chen, Longtao Huangfu, Xuelian Li, Yunyan Gu, Hongli Shan
Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte" 2016, 94 (6): 655-65

UNLABELLED: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and highly lethal fibrotic lung disease with unknown cause or cure. Although some microRNAs (miRNAs), such as miR-26a and let-7d, have been confirmed, the contribution to the pathophysiological processes of IPF, the roles of miRNAs and intrinsic links between them in fibrotic lung diseases are not yet well understood. In this study, we found that Lin28B could induce the process of epithelial-mesenchymal transition (EMT) by inhibiting let-7d, whereas inhibition of Lin28B mitigated TGF-β1-induced fibrogenesis and attenuated EMT in both cultured A549 cells and MLE-12 cells. More importantly, over-expression of miR-26a could simultaneously enhance the expression of let-7d in A549 cells, and further study confirmed that Lin28B was one of the direct targets of miR-26a, which mediates, at least in part, the regulatory effects of miR-26a on the biogenesis of let-7d. Finally, we constructed a regulatory network among miRNAs involved in the progression of IPF. Taken together, our study deciphered the essential role of Lin28B in the pathogenesis of EMT, and unraveled a novel mechanism that miR-26a is a modulator of let-7d. This study also defines the miRNAs network involved in IPF, which may have implications for developing new strategies for pulmonary fibrosis.

KEY MESSAGE: Upregulation of Lin28B contributes to idiopathic pulmonary fibrosis. Lin28B causes epithelial-mesenchymal transition (EMT) by inhibition of let-7d. Lin28B is one of the targets of microRNA-26a. miR-26a enhances the expression of let-7d via targeting regulation of Lin28B. A regulatory network among miRNAs involved in the progression of IPF.


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