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Long non-coding RNAs (lncRNAs) act as crucial modulators during the development of diverse cancers. Although various types of lncRNAs in prostate cancer (PCa) have been explored, quantities of lncRNAs still wait to be exploited. The present study is to probe the functions and mechanism of lncRNA HOXA cluster antisense RNA 2 (HOXA-AS2) in PCa. In the present study, we discovered that HOXA-AS2 was highly expressed in PCa tissues and cells. HOXA-AS2 depletion obviously influenced cell proliferation, migration, invasion, as well as epithelial-to-mesenchymal transition (EMT) progression. In addition, miR-509-3p had low expression in PCa cells and inversely modulated by HOXA-AS2. Cutting down HOXA-AS2 expression was capable of up-regulating miR-509-3p expression. In addition, HOXA-AS2 served as a competing endogenous RNA (ceRNA) through sponging miR-509-3p to release pre-B-cell leukemia homeobox 3 (PBX3) expression. The expression of PBX3 was noticeably high in tumor tissues. And PBX3 expression level was down-regulated markedly with the knockdown of HOXA-AS2. Rescue experiments certified the facilitated role of HOXA-AS2-miR-509-3p-PBX3 axis in regulating the progress of PCa. The present study may provide clues for exploration of novel therapeutic targets for PCa patients.

LncRNA HOXA-AS2 promotes the progression of prostate cancer via targeting miR-509-3p/PBX3 axis