机构：[1]The Department of Biobank, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China[2]The ThirdDepartment of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China[3]Department ofOral Pathology, Shanghai Jiao Tong University School of Medicine, Shanghai, China[4]National Liver Tissue Bank, Eastern Hepatobiliary SurgeryHospital, Second Military Medical University, Shanghai, China[5]Department of Hepatobiliary Surgery, General Hospital of Southern TheatreCommand, Guangzhou, China[6]Department of Oncology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China[7]Department of General Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Background: N6-methyladenosine (m(6)A) is the most frequent internal methylation of eukaryotic RNA (ribonucleic acid) transcripts and plays an important function in RNA processing. The current research aimed to investigate the role of m(6)A-STIM2 axis in cholangiocarcinoma (CCA) progression. Methods: The expression of STIM2 (Stromal Interaction Molecule 2) in CCA was measured using quantitative polymerase chain reaction (PCR) and immunohistochemistry (IHC). STIM2 was examined in vivo for its effects on the malignant phenotypes of CCA cells. The m(6)A modification of STIM2 was assessed through MeRIP (methylated RNA Immunoprecipitation)-PCR. Results: Based on the GEPIA (Gene Expression Profiling Interactive Analysis) 2 database findings, a low STLM2 mRNA (messenger RNA) level was related to a poor prognosis in individuals with CCA. Quantitative PCR and IHC assays indicated decreased protein satin in CCA tissues and were associated with extrahepatic metastasis. Vianude mice tail vein injection model indicated that increased STIM2 levels suppressed CCA cell metastasis in vivo, while KRT8 (keratin 8) was detected as the direct downstream target of STIM2-mediated CCA cell metastasis in vivo. Meanwhile, based on SRAMP database and MeRIP assays indicated that m(6)A alteration resulted in abnormal STIM2 expression in CCA via METTL14 and YTHDC2. Conclusions: Our findings revealed the epi-transcriptomic dysregulation in CCA and metastasis by proposing a complicated STIM2-KRT8 regulatory paradigm based on m(6)A alteration.
基金：
Science Fund for Creative Research Groups, NSFC, China
(No. 81900550); and the Shanghai Tongren Hospital (No.
2019shtrxx09).
第一作者机构：[1]The Department of Biobank, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
共同第一作者：
通讯作者：
通讯机构：[5]Department of Hepatobiliary Surgery, General Hospital of Southern TheatreCommand, Guangzhou, China[6]Department of Oncology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China[7]Department of General Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China[*1]Department of General Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Zhizaoju Rd. 639, Shanghai 200023, China[*2]Department of Hepatobiliary Surgery, General Hospital of Southern Theatre Command, 111 Liuhua Road, Guangzhou 510010, China.[*3]Department of Oncology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, 1111, Xianxia Road, Shanghai 200336, China.
推荐引用方式(GB/T 7714)：
Chen Feng-Qiu,Zheng Hao,Gu Ting,et al.Modification of STIM2 by m(6)A RNA methylation inhibits metastasis of cholangiocarcinoma[J].ANNALS OF TRANSLATIONAL MEDICINE.2022,10(2):doi:10.21037/atm-21-6485.
APA：
Chen, Feng-Qiu,Zheng, Hao,Gu, Ting,Hu, Yu-Hua,Yang, Le...&Li, Hong-Jie.(2022).Modification of STIM2 by m(6)A RNA methylation inhibits metastasis of cholangiocarcinoma.ANNALS OF TRANSLATIONAL MEDICINE,10,(2)
MLA：
Chen, Feng-Qiu,et al."Modification of STIM2 by m(6)A RNA methylation inhibits metastasis of cholangiocarcinoma".ANNALS OF TRANSLATIONAL MEDICINE 10..2(2022)
