Circ_0060927 regulates miR-331-3p/ERK/MAPK pathway reaction in non-small cell lung cancer through METTL14-driven methylation.

BACKGROUND: Non-coding RNA is one of the most paramount genetic regulators. circRNAs (Circular RNAs) are a potential modulator of various tumors, especially in non-small cell lung cancer (NSCLC). This study focused on elucidating the underlying influence of circ_0060927 on NSCLC progression and relevant regulatory mechanisms. METHODS: Manipulating circ_0060927, MAP2K7, and METTL14 expression in NSCLC cells by lentiviral vectors. The expression of MAP2K7, ERK, p-ERK, p38MAPK, and p-p38MAPK was measured by RT-qPCR and Western Blot experiments. RIP-RT-qPCR was performed to quantify the m6A methylation status of circ_0060927. Cell Counting Kit-8, cell apoptosis assay, wound healing assay, and transwell assay were employed to identify the discrepancy of tumor cells' malignant phenotypes, including cell proliferation, cell motility, and apoptosis. RESULTS: L78 and A549 cells showed high expression of circ_0060927 and its 6A methylation level compared to normal lung epithelial cells. Circ_0060927 could promote tumor cells' proliferation and motility, and reduce cell apoptosis. These effects depended on the m6A methylation derived from METTL14. Besides, circ_0060927 combined miR-331-3p specifically in NSCLC cells to repress its function; simultaneously, miR-331-3p impeded NSCLC cells through suppressing the ERK/MAPK pathway activation by interfering with the expression of MAP2K7 protein. CONCLUSIONS: Circ_0060927 positively regulates NSCLC cells' malignant biological behaviors via targeted binding to miR-331-3p. MiR-331-3p could be recognized as a promising inhibitor for the ERK/MAPK signal pathway in NSCLC cells since it has an interfering effect on MAP2K7 protein. These results cast a meaningful insight into the shadow regarding molecular mechanisms underlying NSCLC and the potential therapeutic perspective of circRNA methylation.