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

Jie, T.; Cai, Q.; Zhao, Y.; Shang, L.; Li, Y.; Zhang, J.; Zhu, L.; Chen, Y.; Li, G.; Liu, Z.; Jia, M.; Kang, S.; Niu, H.; Niu, Y.

2022-09-29 genomics
10.1101/2022.09.28.509879 bioRxiv
Show abstract

Prostate cancer is one of the leading causes of cancer-related deaths in men. While endocrine therapy is effective in the early stage of metastasis, significantly inhibits the progression of metastatic prostate cancer, most patients eventually develop CRPC. Tumor microenvironment are involved in the progression of prostate cancer as an "accomplice", cancer cell-secreted exosomes were identified as crucial messengers can carry lncRNAs to participate in intercellular communication. we revealed PC-3-derived exosomes promote androgen resistance in LNCaP cells. HOXA-AS3 as a ceRNA of miRNA-29b-3p affects the proliferation and invasion ability of prostate cancer cells. A series of molecular experiments, cell experiments and clinical tissue verification experiments confirmed that HOXA-AS3 participates in the castration resistance and progression of prostate cancer through regulating the miR-29b-3p/Mcl-1/STAT3/Cytochrome C/caspases-9 pathway. Dysregulation of HOXA-AS3 is observed in many cancer types, and this study shows the importance of this lncRNA in controlling prostate cancer cell progression, thus highlighting it as a potential biomarker for inhibiting prostate cancer progression and a target for immunotherapy.

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