Hypoxia-induced autophagy reduces radiosensitivity by the HIF-1α/miR-210/Bcl-2 pathway in colon cancer cells

Abstract

Autophagy is an evolutionarily conserved cellular response to conditions of stress such as hypoxia, which induce radioresistance in cancer cells. We studied the mechanism of action of hypoxia on autophagy and radiosensitivity in colon cancer cells. In the human colon cancer cell lines SW480 and SW620, autophagosomes were analyzed to evaluate autophagy by flow cytometry. The expression of hypoxia inducible factor-1α (HIF-1α), Bcl-2, and miR-210 was detected by western blotting and quantitative real-time polymerase chain reaction (PCR). HIF-1α and miR-210 inhibition was induced by siRNA transfections. Apoptosis detection and colony assays were performed to determine radiosensitivity. HIF-1α and miR-210 showed a significant increase under hypoxic condition. The inhibition of HIF-1α decreased miR-210 expression and autophagy. Silencing of miR-210 upregulated Bcl-2 expression and reduced the survival fraction of colon cancer cells after radiation treatment. Under hypoxia, HIF-1α induces miRNA-210 which in turn enhances autophagy and reduces radiosensitivity by downregulating Bcl-2 expression in colon cancer cells. Our results imply that autophagy contributes to the reduction of radiosensitivity in hypoxic environment, and the process is mediated through the HIF-1α/miR-210/Bcl-2 pathway in human colon cancer cells.

Hypoxia induces miR-210, leading to anti-apoptosis in ovarian follicular cells of marine medaka Oryzias melastigma

“…Our results provide another explanation of the impaired reproduction observed in hypoxic fish, in addition to alteration of sex hormone level (Shang et al, 2006). Our finding is concordant with the previous findings that miR-210 plays various roles in cell differentiation, proliferation, and angiogenesis as well as in apoptosis through the post-transcriptional regulation of its downstream effectors under the challenge of hypoxia (Liu et al, 2014b,c;Sun et al, 2015;Zuo et al, 2015). Moreover, we identified an anti-apoptotic role of miR-210 through its downstream effectors, including DLC1, RBM25, TNFRSF10B, USP7, and SLK, in the female reproductive system under hypoxia.…”

Role of microRNA-141 in colorectal cancer with lymph node metastasis

“…Therefore, these results suggest that the alterations in the immune system may be associated with the changes in miRNA-141 and MAP4K4 expression levels, which may contribute to the pathogenesis of CRC. Considering the various factors associated with the pathogenesis of CRC (31)(32)(33), and due to the limited number of subjects enrolled in the present study, further in-depth studies are required to investigate the detailed mechanisms through which miRNA-141 and MAP4K4 are involved in the development of CRC.…”

MicroRNAs Involvement in Radioresistance of Head and Neck Cancer

“…Activation of this pathway results in induction of radioresistance in hepatocellular carcinoma [60]. On the other hand, increased radiosensitivity of hepatic origin tumors has been described after downregulation of miR-210 [61], whereas the same miRNA is also involved in HIF-1 α /Bcl-2 guided radiosensitivity in colon cancer [62]. The close relationship of miR-210 with hypoxia induced cellular processes has been observed also in cervical and breast cancer [63].…”