Silencing of LncRNA PVT1 inhibits the proliferation, migration and fibrosis of high glucose-induced mouse mesangial cells via targeting microRNA-93-5p.

The present study aimed to investigate the regulatory role of long non-coding RNA plasmacytoma variant translocation 1 (PVT1) on high glucose (HG)-induced mouse mesangial cells (MMCs). PVT1 expression in diabetic nephropathy (DN) mice and HG-induced MMCs was detected by qRT-PCR. EdU and Colony formation, Annexin V-PI staining, Muse cell cycle, Scratch, and Transwell assays were performed to detect the cell proliferation, apoptosis, cell cycle, migration, and invasion, respectively. The contents of fibrosis factors in cell-culture supernatants were detected by enzyme-linked immunosorbent assay (ELISA). Western blot was performed to detect the expression of factors involved in apoptosis, cell cycle, migration and invasion, fibrosis, and PI3K/Akt/mTOR pathway. The targeting relation between miR-93-5p and PVT1 was predicted by StarBase3.0 (an online software for analyzing the targeting relationship) and identified by Dual-luciferase reporter (DLR) assay. PVT1 was overexpressed in DN kidney tissues and HG-induced MMCs. HG-induced MMCs exhibited significantly increased EdU-positive cells, cell colonies, S and G2/M phase cells, migration and invasion ability, and contents of fibrosis factors, as well as significantly decreased apoptosis rate compared with NG-induced MMCs. HG significantly up-regulated Bcl-2, CyclinD1, CDK4, N-cadherin, vimentin, Col. IV, FN, TGF-β1 and PAI-1, and down-regulated Bax, cleaved caspase-3, cleaved PARP, and E-cadherin in MMCs. Silencing of PVT1 eliminated the effects of HG in MMCs and blocked PI3K/Akt/mTOR pathway. MiR-93-5p was a target of PVT1, which eliminated the effects of PVT1 on HG-induced MMCs. PVT1 silencing inhibited the proliferation, migration, invasion and fibrosis, promoted the apoptosis, and blocked PI3K/Akt/mTOR pathway in HG-induced MMCs via up-regulating miR-93-5p.

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