The mechanism of lncRNA SNHG12 interacting with ELAVL1 to activate PI3K / AKT signaling pathway to promote docetaxel resistance in prostate cancer cells

Objective Prostate cancer (PCa) is the second most common cancer type in men worldwide, and docetaxel (DTX) resistance is one of the primary factors contributing to poor prognosis. Long non-coding RNAs (lncRNAs) have been reported to play a critical role in PCa DTX resistance, but the role of lncRNA SNHG12 in PCa DTX resistance remains unclear. Therefore, this study aimed to investigate the effect of SNHG12 on PCa DTX resistance and decipher its underlying mechanism. Methods PC-3 cells were treated with gradient DTX to generate DTX-resistant PC-3 cells (PC-3R), and a PCa tumor-bearing model was established by injecting PC-3R cells into the left dorsum of nude mice. The expression of key genes and proteins was detected by RT-qPCR, Western blot, immunofluorescence, and immunohistochemistry. Cell proliferation and migration were evaluated using CCK-8 assays, colony formation assays, and Transwell migration assays. RNA-protein binding was detected by RIP-qPCR. Results SNHG12 was upregulated in PC-3R cells. Knockdown of SNHG12 inhibited the proliferation and migration of PC-3R cells, as well as tumor growth in nude mice. Treatment with 10 nM DTX alone had no significant effect on PC-3R cell proliferation or migration, but knocking down SNHG12 in combination with DTX treatment significantly suppressed PC-3R cell proliferation, migration, and tumor growth. Additionally, ELAVL1 expression was upregulated in PC-3R cells, and the activation level of the PI3K/AKT signaling pathway was increased in both PC-3R cells and tumor tissues. Treatment with the PI3K activator 740 Y-P attenuated the inhibitory effect of SNHG12 knockdown. Importantly, SNHG12 in PC-3R cells was found to bind to ELAVL1. Mechanistic studies revealed that SNHG12 activated the PI3K/AKT signaling pathway by binding to ELAVL1, thereby inducing PCa DTX resistance. Conclusion Our findings demonstrate that SNHG12 knockdown plays a pivotal role in suppressing DTX resistance in PCa, and unravel its underlying molecular mechanism, thereby providing a potential therapeutic target for developing DTX-sensitizing strategies in PCa treatment.