Abstract
Benign prostatic hyperplasia(BPH)is the expansion of the prostate gland that results in urinary symptoms.Both the epithelial-to-mesenchymal transition(EMT)and the Wnt signaling pathway are associated with BPH pathology.In this study,we find that miR-1202 is increased in BPH samples.Overexpression of miR-1202 in TGF-β-treated BPH-1 cells enhances cell survival and DNA synthesis and inhibits cell apoptosis,whereas miR-1202 inhibition partially abolishes the effects of TGF-β on BPH-1 cells.miR-1202 overexpression reduces E-cadherin level but elevates vimentin,N-cadherin,and snail levels,whereas miR-1202 inhibition partially attenuates the effects of TGF-β on EMT markers.Regarding the Wnt/β-catenin pathway,miR-1202 overexpression significantly enhances,whereas miR-1202 inhibition partially decreases,the promotive effects of TGF-β on Wnt1,c-Myc,and cyclin D1 proteins.3-Hydroxy-3-methylglutaryl-CoA lyase(HMGCL)is a direct downstream target of miR-1202,and miR-1202 inhibits HMGCL expression through binding to its3'UTR.Overexpression of HMGCL significantly reduces the effect of miR-1202 overexpression on the phenotypes of BPH-1 cells by inhibiting cell survival and promoting apoptosis.Simi-larly,HMGCL overexpression has the opposite effects on EMT markers and the Wnt/β-catenin signaling,and markedly alleviates the effects of miR-1202 overexpression.Finally,in the BPH rat model,Ki67 and vimentin levels are elevated,but E-cadherin and HMGCL levels are reduced.In conclusion,miR-1202 is upregulated in benign prostatic hyperplasia;miR-1202 enhances epithelial cell proliferation,suppresses cell apoptosis,and promotes EMT by targeting HMGCL.The Wnt/β-catenin pathway may participate in the miR-1202/HMGCL axis-mediated regulation of BPH-1 cell phenotypes.
基金项目
海南省自然科学基金(822MS199)
Hainan Provincial Health Commission Project(20A200032)
Key Science and Technology Project of Haikou City(2022-031)
Finance Science and technology project of Hainan Province(ZDYF2019112)
国家科技期刊平台
NSTL
万方数据