| Objective:microRNAs play an important role in the generation and progress of cancer.It is reported that microRNA-338-3p(miR-338-3p) can inhibit the development of gastric cancer、lung cancer and colon cancer through target gene. However, further investigation is needed to discover the role of miR-338-3p in breast carcinoma and its potential mechanism.In order to adapt to the quick proliferation,breast carcinoma changes the way of glycometabolism,that is despite sufficient oxygen supply,glycolysis is the dominant pathyway for generating ATP. The main purpose of our investigation is to discover the role and potential mechanism of miR-338-3p in the glycolysis of breast carcinoma.Method:Investigate the effect of miR-338-3p on the proliferation of breast carcinoma cell by cell growth curve; explore the migration and invasion of miR-338-3p overexpressed breast carcinoma by cell migration experiment and Transwell test;2.Investigate the effect of miR-338-3p on the glycolysis of breast carcinoma by measuring glucose uptake level and lactate production level, besides, inhibite the glycolysis of breast carcinoma to explore whether miR-338-3p still has effect on it;3.Explore the direct target of miR-338-3p on glycolysis of breast carcinomia by RNA pull-down and mass spectrometry, and verify the consequence in eucell and prokaryotic cell; 4.Knockdown Ago2、Ago3 to investigate whether miR-338-3p still take effect.Result: 1.miR-338-3p can inhibit the proliferation、 migration and invasion of breast carcinoma; 2.miR-338-3p inhibits the glycolysis of breast carcinoma; 3.miR-338-3p inhibits the glycolysis of breast carcinoma by target PKM2; 4.miR-338-3p directly binds to PKM2 inhibiting its activity rather than the normal way which needs Ago and binds to the 3’-UTR domain of PKM2.Conclusion:MiR-338-3p inhibits glycolysis by directly binding to PKM2, so affects the proliferation、migration and invasion of breast carcinoma. |
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