Human MiR-489 Induces Autophagy In Cancer Cells By Targeting P38α

Cancer is one of the major diseases that endanger human health. The incidence of cancer becomes higher and higher, and has a trend attack young adults. Traditional treatments such as surgery, radiotherapy and chemotherapy, etc., can not cure cancer. Recently, more and more researches in different types of tumors indicate that there are cancer stem cells in tumor. These cells are special and play an important role in tumor occurrence, development, resistance to radiotherapy and chemotherapy, metastasis and tumor recurrence. Previous studies have shown that miRNAs is related to the proliferation of cancer cells, differentiation and self-renewal of stem cells and tumor stem cell. For example, miR-489 decreased the survival of ovarian cancer cell SKOV3 and OVCAR3 after cisplatin treatment; miR-489 regulated quiescence of muscle stem cells in mice through targeting DEK; MiR-128 reduced the proliferation of glioma stem cells through targeting Bmi-1 et al. The researches of the miRNA in tumor are of great significance to oncotherapy.In this study, we study the function of miR-489 in tumor, as it is involved in the regulation of quiescence of mouse micro satalite cells. We found that miR-489 could induce autophagy in human fibrosarcoma cell lines HT1080, and verified p38a as target gene of miRNA-489, also involved in the process of the autophagy regulation. After miR-489 overexpression, the protein level of p38a and DEK reduced and the protein level of p53, p-p53 increased. Then we use the virus that express shRNA of p38a and DEK to knockdown p38a and DEK respectively in human fibrosarcoma cell lines HT1080, after siliencing of both genes, the induction of autophagy was also observed respectively. After p38a knockdown, the protein level of DEK decreased and the protein level of p53 increased. After DEK knockdown, the protein level of p53 was also increased. The results indicate that p38a,DEK,p53 regulates autophagy in human fibrosarcoma cell lines HT1080. For further study the regulation of miR-489 in cancer, we sorted gastric cancer stem cells from human gastric cancer cell lines MKN45. After overexpressing miR-489 in gastric cancer stem cells, the protein level of p38a and DEK reduced and the protein level of p53, p-p53 increased and the induction of autophagy was also observed. Moreover, after miR-489 overexpression, the rate of tumor sphere forming was significantly decreased in contrast to the control. We also found label retaintion cells which were in a quiescent state in gastric cancer sphere and analysed the regulation of autophagy. This result indicated that miR-489 may be involved in the regulation of gastric cancer stem cell proliferation or differentiation. Our research provides valuable information for further investigation of the functions of miR-489 in cancer.