lncRNA PFAR Promotes Lung Fibroblast Activation and Fibrosis by Targeting miR-138 to Regulate the YAP1-Twist Axis.

Molecular Therapy : the Journal of the American Society of Gene Therapy
Xiaoguang ZhaoH Liang

Abstract

Long non-coding RNAs (lncRNAs) have been reported to be involved in various pathophysiological processes in many diseases. However, the role and mechanism of lncRNAs in idiopathic pulmonary fibrosis (IPF) have not been explicitly delineated. In the present study, we reported that lncRNA NONMMUT065582, designated pulmonary fibrosis-associated RNA (PFAR), is upregulated in the lungs of mice with lung fibrosis as well as in fibrotic lung fibroblasts. Overexpression of PFAR promoted fibrogenesis through modulation of miR-138, whereas knockdown of PFAR attenuated TGF-β1-induced fibrogenesis in lung fibroblasts. In addition, knockdown of miR-138 promoted fibrogenesis by targeting regulation of yes-associated protein 1 (YAP1), whereas enhanced expression of miR-138 attenuated fibrogenesis in lung fibroblasts. Mechanistically, PFAR acted as competing endogenous RNA (ceRNA) of miR-138: forced expression of PFAR reduced the expression and activity of miR-138 to activate YAP1 and promote fibrogenesis in lung fibroblasts, whereas loss of YAP1 abrogated the pro-fibrotic effect of PFAR. More importantly, PFAR silencing alleviated BLM-induced lung fibrosis in mice. Taken together, the results of our study identified lncRNA PFAR as a new pro-f...Continue Reading

Citations

Jan 16, 2019·Cell Death and Differentiation·Yingzhun ChenHaihai Liang
Jan 18, 2020·International Journal of Molecular Sciences·Marina R Hadjicharalambous, Mark A Lindsay
Sep 30, 2019·Cellular and Molecular Life Sciences : CMLS·Loka R Penke, Marc Peters-Golden
Jul 31, 2020·Technology in Cancer Research & Treatment·Shoudan ZhangWenshi Guo
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Jun 12, 2021·Cell Death & Disease·Tingting ChenHaihai Liang

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