Overexpression of lncRNA SNHG12 promotes docetaxel resistance of prostate cancer cells by activating PI3K/AKT signaling via interacting with ELAVL1
ZHAO Cheng
LI Wen
ZHENG Baoshou
WANG Guangming
XIAO Zhisong
LI Yunpeng
Abstract:Objective To investigate the regulatory role of lncRNA SNHG12 in docetaxel(DTX)resistance of prostate cancer(PCa)cells.Methods Tumor-bearing male BALB/c nude mouse models were stablished by dorsal subcutaneous injection of PC-3 cells or DTX-resistant PC-3(PC-3R)cells,either with or without transfection with sh-SNHG12 prior to the injection(n=5).The expressions of the key genes and proteins in the tumor tissues were detected using RT-qPCR,Western blotting,immunofluorescence staining or immunohistochemistry.The proliferation and migration of the treated cells were evaluated with CCK-8,clone formation and Transwell migration assays.RIP-qPCR technique was used to determine the binding between the RNAs and proteins.Results SNHG12 expression was significantly up-regulated in PC-3R cells.SNHG12 knockdown effectively inhibited proliferation and migration of PC-3R cells in vitro and suppressed tumor growth in nude mice.While 10 nmol/L DTX treatment alone did not significantly affect proliferation or migration of PC-3R cells,its combination with SNHG12 knockdown strongly inhibited cell proliferation and migration both in vitro and in the tumor-bearing mice.The expression of ELAVL1 was obviously up-regulated in PC-3R cells,and increased activation level of PI3K/AKT signaling pathway was detected in both PC-3R cells and the xenografts.The effect of SNHG12 knockdown was significantly weakened by treatment with the PI3K activator 740 Y-P.SNHG12 was found to bind to ELAVL1 in PC-3R cells,and mechanistic studies showed that their binding activated the PI3K/AKT signaling pathway to result in DTX resistance in PCa.Conclusion SNHG12 knockdown inhibits DTX resistance of PCa cells by reducing SNHG12 binding to ELAVL1 to inhibit the activation the PI3K/AKT signaling pathway.
Keywords:prostate cancerdrug resistancedocetaxellncRNA SNHG12ELAVL1PI3K/AKT signaling pathway
Publication Date:2026-01-20
Online Publishing Date:2026-01-22(First online date of this platform, not the publication date of the document)
Pages:8( 183-190 )
