miR-1202 regulates BPH-1 cell proliferation,apoptosis,and epithelial-to-mesenchymal transition through targeting HMGCL  

作　　者：Zhenting Wang Xianlai Yin Peng Yang Binghao Gong Haifang Liu 

机构地区：[1]Department of Urology,Affiliated Haikou Hospital of Xiangya Medical School,Central South University,Haikou 570208,China

出　　处：《Acta Biochimica et Biophysica Sinica》2024年第5期675-687,共13页生物化学与生物物理学报（英文版）

基　　金：supported by the grants from the Natural Science Foundation of Hainan Province,China(No.822MS199);the Hainan Provincial Health Commission Project(No.20A200032);the Key Science and Technology Project of Haikou City(No.2022-031);the Finance Science and Technology Project of Hainan Province(No.ZDYF2019112).

摘　　要：Benign prostatic hyperplasia(BPH)is the expansion of the prostategland that results in urinary symptoms.Both the epithelial-to-mesenchymaltransition(EMT)and the Wnt signaling pathway are associated with BPHpathology.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 survivaland DNA synthesis and inhibits cell apoptosis,whereas miR-1202 inhibitionpartially abolishes the effects of TGF-βon BPH-1 cells.miR-1202 overexpressionreduces E-cadherin level but elevates vimentin,N-cadherin,and snail levels,whereas miR-1202 inhibition partially attenuates the effects of TGF-βon EMTmarkers.Regarding the Wnt/β-catenin pathway,miR-1202 overexpressionsignificantly enhances,whereas miR-1202 inhibition partially decreases,thepromotive effects of TGF-βon Wnt1,c-Myc,and cyclin D1 proteins.3-Hydroxy-3-methylglutaryl-CoA lyase(HMGCL)is a direct downstream target ofmiR-1202,and miR-1202 inhibits HMGCL expression through binding to its 3′UTR.Overexpression of HMGCL significantly reduces the effect of miR-1202overexpression on the phenotypes of BPH-1 cells by inhibiting cell survival andpromoting apoptosis.Similarly,HMGCL overexpression has the opposite effects onEMT markers and the Wnt/β-catenin signaling,and markedly alleviates the effectsof miR-1202 overexpression.Finally,in the BPH rat model,Ki67 and vimentinlevels are elevated,but E-cadherin and HMGCL levels are reduced.In conclusion,miR-1202 is upregulated in benign prostatic hyperplasia;miR-1202 enhancesepithelial cell proliferation,suppresses cell apoptosis,and promotes EMT bytargeting HMGCL.The Wnt/β-catenin pathway may participate in the miR-1202/HMGCLaxis-mediated regulation of BPH-1 cell phenotypes.

关 键 词：benign prostate hyperplasia(BPH) epithelial-to-mesenchymal transition(EMT) Wnt/β-catenin pathway miR-1202 3-hydroxy-3-methylglutaryl-CoA lyase(HMGCL) 

分 类 号：R697.32[医药卫生—泌尿科学]