A-to-I RNA Editing Endows miR-3664-5p with Carcinogenicity in Breast Cancer Through Modulating LONP2 Mediated Glycolysis.

Abstract

Breast cancer has become the main cause threatening women's health. RNA editing is one of the most important mechanisms for modifying genetic information. This study explained the relationship between A-to-I RNA edited miR-3664-5p and malignant phenotype of breast cancer. The results showed that high editing level of miR-3664-5p in breast cancer, which was related to tumor stage, recurrence and prognosis of breast cancer patients. ADAR perturbation experiments demonstrated that ADAR1 is the key enzyme regulating miR-3664-5p editing in breast cancer. A series of in vitro assays revealed that miR-3664-5p functioned as a tumor suppressor in breast cancer, but ed-miR-3664-5p promoted breast cancer development. Mechanically, dual-luciferase reporter assay confirmed that ed-miR-3664-5p directly targets LONP2, yet wt-miR-3664-5p loss this binding site. ChIP assay proved that PKM2 was enriched in the transcriptional regulatory region of LONP2 gene. Seahorse XFe analysis showed that LONP2 knockdown strengthened glycolysis in breast cancer. Xenograft assay also demonstrated that edited miR-3664-5p affected glycolysis in breast cancer through the regulation of LONP2. In conclusion, A-to-I RNA editing endows miR-3664-5p with carcinogenicity in breast cancer through modulating LONP2 mediated glycolysis.