Targeting SNHG3/miR-186-5p reverses the increased m6A level caused by platinum treatment through regulating METTL3 in esophageal cancer
Mingxin Zhang, Minghua Bai, Li Wang, Ning Lü, Jia Wang, Rong Yan, Manli Cui, Honglin Yan, Lingmin Zhang
Abstract
BACKGROUND: Platinum-based chemotherapy is a mainstay for treating esophageal cancer patients. In this manuscript, we have provided clues for influence of platinum on overall m6A level and further investigated the potential regulatory mechanism. METHODS: qRT-PCR was used to measure SNHG3 and miR-186-5p expression; ELISA and western blot were used to measure the expression of METTL3. CCK8 was used to measure the cell proliferation rate. Caspase 3/7 activity was used to measure the apoptosis rate. Dual luciferase reporter gene assay and RNA pull down assay were used to investigate the potential crosstalk between miR-186-5p and SNHG3; and miR-186-5p and METTL3. RESULTS: m6A level was increased when treated with platinum (CDDP, CPB and L-OHP). Besides, SNHG3 expression was induced and miR-186-5p expression was suppressed by platinum. Furthermore, SNHG3 could promote the m6A level, however miR-186-5p inhibited the m6A level through targeting METTL3. SNHG3 interacts with miR-186-5p to negatively regulate the expression of miR-186-5p; and miR-186-5p might bind to the 3'UTR of METTL3 to regulate its expression. CONCLUSION: Platinum can increase the overall m6A level of esophageal cancer. SNHG3/miR-186-5p, induced by platinum, was involved in regulating m6A level by targeting METTL3. Our manuscript has provided clues that regulating m6A level might be a novel way to enhance the platinum efficacy.