[Overexpression of lncRNA SNHG12 promotes docetaxel resistance of prostate cancer cells by activating PI3K/AKT signaling via interacting with ELAVL1].

OBJECTIVES: 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. CONCLUSIONS: SNHG12 knockdown inhibits DTX resistance of PCa cells by reducing SNHG12 binding to ELAVL1 to inhibit the activation the PI3K/AKT signaling pathway.