MiR-489-3p reduced pancreatic cancer proliferation and metastasis by targeting PKM2 and LDHA involving glycolysis
Abstract Background: Malignant proliferation and chemotherapy resistance are some of the causes of high mortality in pancreatic cancer. MicroRNAs have for a long period been a hot spot in cancer research and are involved in tumor formation and metabolic stress responses. miR-489-3p is involved in the inhibition of the growth of many tumors. However, its relationship with the growth and metabolism of pancreatic cancer is not clear.Methods:We used RNA in situ hybridization to analyze the differential expression of miR-489-3p in pancreatic cancer tissues and adjacent tissues. The qRT-PCR experiment detected the content of miR-489-3p in pancreatic cancer cell lines and ordinary pancreatic ductal epithelial cells. Then we did experiments in vivo (subcutaneous tumor formation in nude mice) and in vitro (plate cloning, transwell, glycolysis related experiments) experiments to verify that miR-489-3p can continue the invasion and metastasis of pancreatic cancer and glucose metabolism. Furthermore, we confirmed that LDHA and PKM2 are the two targets of miR-489-3p through dual luciferase reporter gene experiments. Finally, several reply experiments were done to verify the regulation mechanism of miR-489-3p.Results: We determined that miR-489-3p was under-expressed in pancreatic cancer tissues by RNA in situ hybridization. The function acquisition and deletion and glycolysis experiments confirmed that miR-489-3p could inhibit the proliferation and invasion of Glycolysis. On the analysis of the website, we found that miR-489-3p could target LDHA and PKM, a finding that we verified through the luciferase report experiment. Therefore, we proceeded with recovery experiments on LDHA and PKM2 and concluded that miR-489-3p performed its function by targeting LDHA and PKM2. Finally, in vivo experiments confirmed that highly expressed miR-489-3p inhibited the growth of pancreatic cancer.Conclusion: In short, this study has identified miR-489-3p as a novel chemotherapy target for pancreatic cancer, but its diagnostic value deserves further study.