Exosome-derived lncRNA HOXA-AS3 promotes castration resistance and progression of prostate cancer via the miR-29b-3p/Mcl-1/STAT3 axis

Background: Tumor microenvironment are involved in the progression of prostate cancer as an "accomplice", and cancer cell–secreted exosomes were identified as crucial messengers can carry lncRNAs to participate in intercellular communication. Herein, we report that an lncRNA HOXA-AS3, was correlated positively with the castration resistance and progression of prostate cancer. Methods Indirect co-culture of PC-3 and LNCaP was performed to explore the androgen resistance of prostate cancer. MTT, colony formation test, exosome isolation, identification and uptake test, and western blot confirmed that exosomes promote androgen resistance in LNCaP cells. Further, the molecular mechanism of HOXA-AS3 was proved by bioinformation analysis, Dual-Luciferase Reporter Gene Assays, gene knockout and overexpression experiment, cell proliferation and apoptosis experiment, qPCR, immunofluorescence experiment and rescue experiment. Finally, rats xenografts and prostate tissue section were used to examine the role of HOXA-AS3 in the transformation of ADPC into CRPC. Results Exosome-derived lncRNA HOXA-AS3 promotes the proliferation, migration, invasion and hormone resistance of prostate cancer cells. HOXA-AS3 functions as a competing endogenous RNAs (ceRNA) for miRNA-29b-3p, thereby elevating Mcl-1 and STAT3 expression, inhibiting the release of cytochrome c and the activation of Caspases-9, resulting in the decrease of hormone sensitivity, and finally leads to androgen resistance and progression of prostate cancer. Conclusions lncRNA HOXA-AS3 participates in the castration resistance and progression of prostate cancer through regulating the miR-29b-3p/Mcl-1/STAT3 pathway. lncRNA HOXA-AS3 might have the potential to serve as a candidate intervention targets for prostate cancer treatment.