SUMO1 modification of methyltransferase-like 3 promotes tumor progression via regulating Snail mRNA homeostasis in hepatocellular carcinoma
Rationale:Hepatocellular carcinoma(HCC)is one of the leading causes of mortality worldwide.Methyltransferase-like 3(Mettl3),an RNA N6-methyladenosine(m6A)methyltransferase,has been shown to act as an oncogene in several human cancers.However,the regulatory role of posttranslational modifications of Mettl3 in liver cancer remains elusive.Methods:SUMOylation was analyzed using immunoprecipitation and western blot assays.In vitro and in vivo biological functions were examined using MTS,colony formation,wound healing,transwell,apoptosis,and viability assays and the BALB/c nude mouse model,respectively.Immunohistochemistry was conducted to evaluate the prognostic value of Mettl3 expression in HCC.The regulatory mechanism of Mettl3 in HCC was investigated by m6A dot blot,immunofluorescence,dual luciferase reporter,protein stability,and RNA stability assays.Results:Mettl3 was found to be SUMOylated by a small ubiquitin-like modifier SUMO1.Further,SUMOylation of Mettl3 was increased upon mitogen stimulation,which correlated with UBC9 upregulation,and was positively correlated with high metastatic potential of liver cancer.Finally,SUMOylation of Mettl3 was found to regulate HCC progression via controlling Snail mRNA homeostasis in an m6A methyltransferase activity-dependent manner.Conclusions:This study revealed a novel mechanism of SUMOylated Mettl3-mediated Snail mRNA homeostasis,identifying the UBC9/SUMOylated Mettl3/Snail axis as a novel mediator of the SUMO pathway involved in HCC progression.
Hepatocellular carcinoma N6-methyladenosine SUMOylations Mettl3 Snail
Hongfa Xu Hao Wang Wei Zhao Sirui Fu Yong Li Wenjun Ni Yongjie Xin Wei Li Chenzi Yang Yanyan Bai Meixiao Zhan Ligong Lu
Zhuhai Interventional Medical Center,Zhuhai Precision Medical Center,Jinan University,Zhuhai People' Department of urinary surgery,Jinan University,Zhuhai People's Hospital,Zhuhai,Guangdong,519000,Chin School of Stomatology,Changsha Medical University,Changsha City,Hunan,410219,China
国际会议
第三届暨南大学粤港澳大湾区医学与健康发展分论坛——医学研究生学术论坛
广州
英文
405-420
2020-11-28（万方平台首次上网日期，不代表论文的发表时间）