MiR-30a and miR-205 are downregulated in hypoxia and modulate radiosensitivity of prostate cancer cells by inhibiting autophagy via TP53INP1.

OBJECTIVE: MiR-30a and miR-205 are two miRNAs downregulated in prostate cancer and are involved in autophagy regulation. However, how they are downregulated in prostate cancer is still not clear. In this study, we firstly investigated the association between miR-30a and miR-205 downregulation and hypoxia in prostate cancer. Then, we further investigated the regulative effect of miR-30a on TP53INP1 and autophagy-related radiosensitivity of process cancer cells.
MATERIALS AND METHODS: The expression change of miR-30a, miR-205 and Dicer after hypoxic treatment were measured in DU145 and LNCaP cells. The effect of miR-30a and miR-205 on irradiation-induced autophagy and radiosensitivity of the cancer cells were also explored. The regulative effect of miR-30a on TP53INP1 expression and the effect of miR-30a/miR-205/TP53INP1 axis on autophagy and radiosensitivity regulation were further studied.
RESULTS: MiR-30a and miR-205 were downregulated under hypoxia as a result of impaired Dicer expression in DU145 and LNCaP cells. Enforced miR-30a and miR-205 expression attenuated irradiation-induced autophagy and also sensitized the cells to irradiation. Dual luciferase assay and following Western blot analysis showed that miR-30a directly targets 3'UTR of TP53INP1 and decreases its expression at protein level. Both miR-30a and miR-205 modulate radiosensitivity of prostate cancer cells at least via TP53INP1.
CONCLUSIONS: This study revealed that miR-30a and miR-205 are two hypoxia responsive miRNAs, which simultaneously target TP53INP1 and suppress its expression. The miR-30a/miR-205/TP53INP1 axis is involved in autophagy and radiosensitivity regulation, which represents a potential therapeutic target for the treatment of prostate cancer.