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

pubmed: wnt1 2024-07-19

Acta Biochim Biophys Sin (Shanghai). 2024 May 25;56(5):675-687. doi: 10.3724/abbs.2024001.

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 its 3'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. Similarly, 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.

PMID:38551020 | PMC:PMC11177111 | DOI:10.3724/abbs.2024001