IncRNASNHG12与ELAVL1相互作用激活PI3K/AKT信号通路促进前列腺癌细胞多西他赛的耐药机制

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Abstract：ObjectiveToinvestigatetheregulatoryroleofIncRNASNHG12indocetaxel（DTX）resistanceof prostatecancer （PCa）cell.MethodsTumor-bearingmaleBALB/cnudemousemodelswerestablishedbydorsalsubcutaneous injectionof PC-3cellsorDTX-resistantPC-3（PC-3R）cels，eitherwithowithouttransfectionwithsh-SNHG12priortotheinjection （n=5） The expressions of the key genesand proteinsinthe tumor tisses were detected using RT-qPCR，Western bloting， immunofluorescencestainingorimmunohistochemistry.Theproliferationandmigrationofthetreatedcelswereevaluated withCCK-8，clonformationandTranswellmigrationassys.RIP-qPCRtechniquewasusedtodeterminethebindingbetween theRNAs and proteins.ResultsSNHG12 expression was significantlyup-regulated in PC-3Rcells.SNHG12 knockdown efectively inhibited proliferationand migrationof PC-3Rcels invitroand suppressd tumor growth innude mice.While10 nmol/L DTX treatment alonedidnot significantlyafectproliferation or migrationof PC-3Rcels，itscombination with SNHG12knockdownstrongly inhibited cellproliferation and migrationboth in vitroand inthetumor-bearing mice.The expresion of ELAVL1 wasobviouslyup-regulated in PC-3R cels，and increasedactivation level of PI3K/AKT signaling pathwaywasdetected inbothPC-3Rcelsand thexenografts.The efectofSNHG12 knockdown wassignificantlyweakened bytreatment withthePI3Kactivator740Y-PSNHG12wasfoundtobindtoELAVL1inPC-3Rcels，andmechanisticstudies showedthattheirbindingactivatedthePI3K/AKTsignaling pathway toresultinDTXresistance inPCa.Conclusion SNHG12 knockdown inhibits DTX resistanceof PCa cels by reducing SNHG12 binding to ELAVL1 toinhibit the activation the PI3K/ AKT signaling pathway.

Keywords： prostate cancer; drug resistance; docetaxel; IncRNA SNHG12; ELAVL1; PI3K /AKT signaling pathway

前列腺癌（PCa）是男性第2大常见肿瘤类型，也是全球癌症死亡相关的第8大原因①。（剩余16220字）