Dataset Information

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

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-?1-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-fibrotic molecule that acts as a ceRNA of miR-138 during lung fibrosis and demonstrated PFAR as a novel therapeutic target for the prevention and treatment of lung fibrosis.

SUBMITTER: Zhao X

PROVIDER: S-EPMC6127506 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Zhao Xiaoguang X Sun Jian J Chen Yingzhun Y Su Wei W Shan Huitong H Li Yue Y Wang Yining Y Zheng Nan N Shan Hongli H Liang Haihai H

Molecular therapy : the journal of the American Society of Gene Therapy 20180627 9

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 thr ...[more]

PMID: 30025992

Similar Datasets

Project description:Long noncoding RNA (lncRNAs) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been reported in diabetic nephropathy (DN) about its effect on podocyte function and cell heat shock induced by hyperglycemia. However, the biological mechanism of MALAT1 regulating DN fibrosis needs further study. In this study, SD rats were administrated with streptozotocin (STZ) to establish a diabetes model. In vitro, human renal tubular epithelial cells (HK-2 and 293T) were treated with high glucose (HG). Here, we found that MALAT1 was upregulated in renal tissues of diabetic rats and HG-treated cells, and HG treatment promoted cell proliferation and invasion. MALAT1 overexpression aggravated protein levels of collagen I (col I), collagen IV (col IV), fibronectin (FN), and laminin (LN) in HK-2 cells, while MALAT1 knockdown exerted the opposite effect. Moreover, the luciferase reporter gene and pull-down assays demonstrated that MALAT1 interacted with miR-2355-3p. The miR-2355-3p level was downregulated in diabetic rats and HG-treated cells, and MALAT1 overexpression inhibited the miR-2355-3p level. Bioinformatics prediction and luciferase reporter gene assay revealed that interleukin 6 signal transducer (IL6ST) was a target of miR-2355-3p. In addition, miR-2355-3p overexpression attenuated fibrosis-related gene levels in HG-treated cells by inhibiting IL6ST expression and inactivating the recombinant signal transducer and activator of the transcription 3 (STAT3) signaling pathway. Knockdown of miR-2355-3p reversed the inhibitory effect of MALAT1 knockdown on IL6ST, col I, col IV, FN, and LN protein levels in HG-induced cells. Overexpression of MALAT1 aggravated cell damage in HG-induced cells via the miR-2355-3p/IL6ST/STAT3 signaling pathway. Finally, enhanced renal fibrosis and kidney tissue damage were observed in diabetic rats. In conclusion, MALAT1 overexpression may enhance renal fibrosis in diabetic rats and cell damage in HG-induced HK-2 cells via the miR-2355-3p/IL6ST axis, which provides a new perspective of DN treatment.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets