Tao Fu1, Ke Ji1, Li Jin2, Ji Zhang1, Xiaojiang Wu1, Xin Ji1, Biao Fan1, Ziyu Jia1, Anqiang Wang1, Jiaen Liu1, Zhaode Bu3, Jiafu Ji4. 1. Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, No. 52 Fucheng Road, Haidian District, Beijing, 100142, China. 2. Department of Radiotherapy, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610041, China. 3. Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, No. 52 Fucheng Road, Haidian District, Beijing, 100142, China. buzhaode@cjcrcn.org. 4. Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, No. 52 Fucheng Road, Haidian District, Beijing, 100142, China. jijiafu@hsc.pku.edu.cn.
Abstract
BACKGROUND: Long non-coding RNA (lncRNA) ASB16 antisense RNA 1 (ASB16-AS1) is recognized as an oncogene in several cancer types, but its relation to GC is unknown. Tripartite motif containing 37 (TRIM37) has been proven to accelerate the development of gastric cancer (GC), whereas the molecular mechanism assisted ASB16-AS1 and TRIM37 in regulating GC progression remains unclear. METHODS: Differentially expressed lncRNAs in GC samples were analyzed based on Gene Expression Omnibus (GEO) data. CCK-8 and colony formation assays were applied to determine the proliferative ability of GC cells. Stem cell-like phenotype of GC cells was assessed by sphere formation assay and flow cytometry analysis. Luciferase reporter assay, RNA immunoprecipitation (RIP), pulldown, and co-immunoprecipitation (Co-IP) were performed to verify the interplay of RNA molecules. RESULTS: ASB16-AS1 was upregulated in GC samples according to GEO data and qRT-PCR analysis. ASB16-AS1 strengthened the proliferative ability and stem cell-like characteristics in GC cells. More importantly, ASB16-AS1 encouraged GC cell growth in vivo. Mechanistically, ASB16-AS1 strengthened TRIM37 expression by sequestering miR-3918 and miR-4676-3p. ASB16-AS1 activated NF-kappa B (NF-κB) pathway by cooperating with ATM serine/threonine kinase (ATM) to induce TRIM37 phosphorylation. CONCLUSION: In summary, ASB16-AS1 exerted oncogenic functions in GC through modulating TRIM37 expression at both mRNA and protein levels.
BACKGROUND: Long non-coding RNA (lncRNA) ASB16 antisense RNA 1 (ASB16-AS1) is recognized as an oncogene in several cancer types, but its relation to GC is unknown. Tripartite motif containing 37 (TRIM37) has been proven to accelerate the development of gastric cancer (GC), whereas the molecular mechanism assisted ASB16-AS1 and TRIM37 in regulating GC progression remains unclear. METHODS: Differentially expressed lncRNAs in GC samples were analyzed based on Gene Expression Omnibus (GEO) data. CCK-8 and colony formation assays were applied to determine the proliferative ability of GC cells. Stem cell-like phenotype of GC cells was assessed by sphere formation assay and flow cytometry analysis. Luciferase reporter assay, RNA immunoprecipitation (RIP), pulldown, and co-immunoprecipitation (Co-IP) were performed to verify the interplay of RNA molecules. RESULTS:ASB16-AS1 was upregulated in GC samples according to GEO data and qRT-PCR analysis. ASB16-AS1 strengthened the proliferative ability and stem cell-like characteristics in GC cells. More importantly, ASB16-AS1 encouraged GC cell growth in vivo. Mechanistically, ASB16-AS1 strengthened TRIM37 expression by sequestering miR-3918 and miR-4676-3p. ASB16-AS1 activated NF-kappa B (NF-κB) pathway by cooperating with ATM serine/threonine kinase (ATM) to induce TRIM37 phosphorylation. CONCLUSION: In summary, ASB16-AS1 exerted oncogenic functions in GC through modulating TRIM37 expression at both mRNA and protein levels.
Authors: Ran Xu; Xuan Zhu; Fangzhi Chen; Changkun Huang; Kai Ai; Hongtao Wu; Lei Zhang; Xiaokun Zhao Journal: Cancer Cell Int Date: 2018-03-20 Impact factor: 5.722
Authors: Johnny M Tkach; Reuben Philip; Amit Sharma; Jonathan Strecker; Daniel Durocher; Laurence Pelletier Journal: Elife Date: 2022-06-27 Impact factor: 8.713