title: Aberrant overexpression of ADAR1 promotes gastric cancer progression by activating mTOR/p70S6K signaling.
abstract: ADAR1, one of adenosine deaminases acting on RNA, modulates RNA transcripts through converting adenosine (A) to inosine (I) by deamination. Emerging evidence has implicated that ADAR1 plays an important role in a few of human cancers, however, its expression and physiological significance in gastric cancer remain undefined. In the present study, we demonstrated that ADAR1 was frequently overexpressed in gastric cancer samples by quantitative real-time PCR analysis. In a gastric cancer tissue microarray, ADAR1 staining was closely correlated with tumor stage (P < 0.001) and N classification (P < 0.001). Functional analysis indicated that ADAR1 overexpression promoted cell proliferation and migration in vitro, whereas ADAR1 knockdown resulted in an opposite phenotypes. Furthermore, ADAR1 knockdown also inhibited tumorigenicity and lung metastasis potential of gastric cancer cells in nude mice models. Mechanistically, ADAR1 expression had a significant effect on phosphorylation level of mTOR, p70S kinase, and S6 ribosomal protein, implying its involvement in the regulation of mTOR signaling pathway. We conclude that ADAR1 contributes to gastric cancer development and progression via activating mTOR/p70S6K/S6 ribosomal protein signaling axis. Our findings suggest that ADAR1 may be a valuable biomarker for GC diagnosis and prognosis and may represent a new novel therapeutic opportunities.
authors.affiliation: Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Dou
authors.affiliation: Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
authors.forename: Shijun
authors.initials: S
authors.lastname: Yu
authors.affiliation: Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Ye
authors.affiliation: Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Yang
authors.affiliation: Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China.|Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
authors.forename: Yandong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Gao
mesh_terms: D000243:Adenosine Deaminase / Q000502:physiology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D016601:RNA-Binding Proteins / Q000502:physiology*; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013274:Stomach Neoplasms / Q000209:etiology* / Q000473:pathology; D058570:TOR Serine-Threonine Kinases / Q000502:physiology*
chemical_list: D016601:RNA-Binding Proteins; C546842:MTOR protein, human; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; C000595356:ADAR protein, human; D000243:Adenosine Deaminase
keywords: ADAR1; gastric cancer; mTOR; metastasis; tumorigenecity