miR-409-3p sensitizes colon cancer cells to oxaliplatin by inhibiting Beclin-1-mediated autophagy.

The chemoresistance of colon cancer cells limits the efficacy of chemotherapy. miR-409-3p has been shown to be downregulated in various types of cancer. In the present study, we examined the role of miR-409-3p in colon cancer as well as the effects of miR­409-3p on the sensitivity of colon cancer cells to oxaliplatin. The expression of miR-409 was significantly downregulated in the human colon cancer cell lines compared with the normal colon epithelial cells. Importantly, the miR-409-3p expression levels were lower in human colon cancer patient samples than in normal colon tissues. Moreover, we observed a negative correlation between the miR­409-3p levels and resistance to oxaliplatin: the oxaliplatin-resistant colon cancer cells exhibited significantly downregulated miR­409-3p levels, but higher autophagic activity than the oxaliplatin-sensitive cells. Using bioinformatics analysis, we predicted that miR­409-3p miRNA binds to the key autophagy gene encoding Beclin-1. Our findings indicated that the overexpression of miR­409-3p inhibited Beclin-1 expression and autophagic activity by binding to the 3'-untranslated region of Beclin-1 mRNA. In addition, the overexpression of miR­409-3p enhanced the chemosensitivity of the oxaliplatin-sensitive and oxaliplatin-resistant colon cancer cells. The restoration of Beclin-1 abrogated these effects of miR­409-3p. In a xenograft model using nude mice, we examined the effects of miR­409-3p on tumor growth during chemotherapy. miR­409-3p overexpression sensitized the tumor to chemotherapy, while inhibiting chemotherapy-induced autophagy in a manner dependent on Beclin-1. The findings of our study suggest that miR-409-3p is capable of enhancing the chemosensitivity of colon cancer cells by inhibiting Beclin-1-mediated autophagy.

MicroRNA-216a enhances the radiosensitivity of pancreatic cancer cells by inhibiting beclin-1-mediated autophagy.

Radioresistance has become a challenge in the treatment of pancreatic cancer, which limits the efficacy and outcomes of radiotherapy in clinical treatment. Autophagy, recognized as an adaptive response to cell stress, has recently been involved in the radioresistance of cancer cells. MicroRNAs (miRNAs) are also involved in the radioresistance of pancreatic cancer cells. In the present study, we established a radioresistant pancreatic cancer cell line and found that miRNA-216a was significantly downregulated whereas the autophagy activity was increased as compared with the control. Forced expression of miR-216a was found to inhibit the expression of beclin-1, a critical autophagic gene, as well as autophagy. Using bioinformatics analysis and the dual-luciferase reporter gene assay, we found that miR-216a directly interacted with 3'-untranslated region (UTR) of beclin-1. Furthermore, the forced expression of miR­216a inhibited cell growth and colony formation ability and promoted the cell apoptosis of radioresistant pancreatic cancer cells in response to irradiation. By contrast, overexpression of beclin-1 abrogated the effects of miR-216a. Furthermore, miR-216a sensitized xenograft tumor to irradiation treatment and inhibited irradiation-induced autophagy by regulating beclin-1. Collectively, the results demonstrated that miR­216a enhanced the radiosensitivity of pancreatic cancer cells by inhibiting beclin-1-mediated autophagy, suggesting a promising molecular target for improving the radiotherapy of pancreatic cancer.