Hypoxia-responsive miR-124 and miR-144 reduce hypoxia-induced autophagy and enhance radiosensitivity ofprostatecancer cells via suppressing PIM1.

Abstract

Cancer cells in hypoxia usually make adaptive changes in cellular metabolism, such as altered autophagy. This might be a cause of enhanced radioresistance in some types of cancer. In this study, we investigated hypoxia‐responsive miRNAs in two prostate cancer cell lines (DU145 and PC3). This study firstly reported that hypoxia induces further downregulation of miR‐124 and miR‐144, which might be a result of impaired dicer expression. These two miRNAs can simultaneously target 3′UTR of PIM1. Functional study showed that miR‐124 or miR‐144 overexpression can inhibit hypoxia‐induced autophagy and enhance radiosensitivity at least via downregulating PIM1. Therefore, hypoxia induced miR‐124 and miR‐144 downregulation may contribute to a prosurvival mechanism of prostate cancer cells to hypoxia and irradiation at least through attenuated suppressing of PIM1. This finding presents a potential therapeutic target for prostate cancer.