miR‐103a‐2‐5p/miR‐30c‐1‐3p inhibits the progression of prostate cancer resistance to androgen ablation therapy via targeting androgen receptor variant 7

Abstract Androgens and androgen receptors are vital factors involved in prostate cancer progression, and androgen ablation therapies are commonly used to treat advanced prostate cancer. However, the acquisition of androgen ablation therapy resistance remains a challenge. Recently, androgen receptor splicing variants lacking the ligand‐binding domain have been reported to play a critical role in the acquisition of androgen ablation therapy resistance. In the present study, we revealed that the messenger RNA expression and the protein levels of an androgen receptor variant 7 (AR‐V7) were higher in prostate cancer tissue samples and in the AR‐positive prostate cancer cell line, VCaP. In contrast, microRNA (miR)‐30c‐1‐3p/miR‐103a‐2‐5p expression was significantly downregulated in tumor tissues and cells. miR‐30c‐1‐3p/miR‐103a‐2‐5p overexpression could inhibit AR‐V7 expression, suppress VCaP cell growth, and inhibit AR‐V7 downstream factor expression by directly targeting the 3′‐untranslated region of AR‐V7. Under enzalutamide (Enza) treatment, the effects of AR‐V7 overexpression were the opposite of those of miR‐103a‐2‐5p/miR‐30c‐1‐3p overexpression; more importantly, the effects of miR‐103a‐2‐5p/miR‐30c‐1‐3p overexpression could be significantly reversed by AR‐V7 overexpression under Enza. In summary, we demonstrated a novel mechanism of the miR‐30c‐1‐3p/miR‐103a‐2‐5p/AR‐V7 axis modulating the cell proliferation of AR‐positive prostate cancer cells via AR downstream targets. The clinical application of miR‐30c‐1‐3p/miR‐103a‐2‐5p needs further in vivo validation.