The pseudogene PTENP1 regulates smooth muscle cells as a competing endogenous RNA

The lncRNA PTENP1 is a pseudogene of phosphatase and tensin homolog deleted on chromosome ten (PTEN), has been implicated in smooth muscle cell (SMC) proliferation and apoptosis. PTENP1 is the pseudogene of PTEN. However, it is unclear whether and how PTENP1 functions in the proliferation and apoptosis of human aortic smooth muscle cells (HASMCs). Here, we hypothesized that PTENP1 inhibits HASMC proliferation and enhances apoptosis by promoting PTEN expression. PCR analysis and Western blot assays respectively showed that both PTENP1 and PTEN were upregulated in human aortic dissection(AD) samples. PTENP1 overexpression significantly increased the protein expression of PTEN, promoted apoptosis and inhibited the proliferation of HASMCs. PTENP1 silencin exhibited the opposite effects and mitigated H2O2-induced apoptosis of HASMCs. In an angiotensin II-induced mouse aortic aneurysm(AA) model, PTENP1 overexpression potentiated aortic SMC apoptosis, exacerbated aneurysm formation. Mechanistically, RNA pull-down assay and luciferase assays using miR-21 mimics or inhibitors  identified PTENP1 as a molecular sponge for miR-21 to endogenously compete for the binding between miR-21 and the PTEN transcript, releasing PTEN expression. This finding was further supported by in vitro immunofluorescent evidence showing decreased cell apoptosis upon miR-21 mimic administration under baseline PTENP1 overexpression. Ex vivo rescue of PTEN significantly mi...

Source: Clinical Science - June 23, 2019 Category: Biomedical Science Authors: Lai, Y., Li, J., Zhong, L., He, X., Si, X., Sun, Y., Chen, Y., Zhong, J., Hu, Y., Li, B., Liao, W., Liu, C., Liao, Y., Xiu, J., Bin, J. Tags: PublishAheadOfPrint Source Type: research