Targeting SNHG3/miR-186-5p reverses the increased m6A level caused by platinum treatment through regulating METTL3 in esophageal cancer

Cancer Cell International

Lingmin Zhang¹  Honglin Yan²  Rong Yan²  Jia Wang²  Mingxin Zhang²  Manli Cui²  Ning Lu²  Minghua Bai³  Li Wang⁴ 

[1] Department of Anesthesiology, The First Affiliated Hospital of Xi’an Jiaotong University, No. 277 Yanta West Road, 710061, Xi’an, Shaanxi, China;Department of Gastroenterology, The First Affiliated Hospital of Xi’an Medical University, No. 48 Feng Hao West Road, 710077, Xi’an, Shaanxi, China;Department of Health, Liaocheng People’s Hospital, 252000, Liaocheng, Shandong, China;Department of Scientific Research, The First Affiliated Hospital of Xi’an Medical University, Xi’an, Shaanxi, China;

关键词: m6A level;    METTL3;    SNHG3;    miR-186-5p;    Platinum;   

DOI  :  10.1186/s12935-021-01747-9

来源: Springer

【 摘 要 】

BackgroundPlatinum-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.MethodsqRT-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.Resultsm6A 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.ConclusionPlatinum 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.

【 授权许可】

CC BY