title: miR-935 suppresses gastric signet ring cell carcinoma tumorigenesis by targeting Notch1 expression.
abstract: Gastric signet ring cell carcinoma (GSRCC) is a unique pathological type of gastric carcinoma that is extremely invasive and has a poor prognosis. Expression of microRNAs (miRNAs) has been closely linked to the carcinogenesis of gastric cancer and has been considered as a powerful prognostic marker. The function of miR-935 has never been reported in cancer before. We found, using microRNA array, that expression of miR-935 in GSRCC cell lines is lower than in non-GSRCC cell lines, and enhanced expression of miR-935 in GSRCC cell-lines inhibit cell proliferation, migration and invasion. We also identified Notch1 as a direct target of miR-935. Knockdown of Notch1 reduced proliferation, migration/invasion of GSRCC cells, and overexpression Notch1's activated form (Notch intracellular domain) could rescue miR-935's tumor suppressive effect on GSRCC. Expression of miR-935 was lower in gastric carcinoma tissue than in paired normal tissue samples, and lower in GSRCC than in non-GSRCC. Our results demonstrate the inverse correlation between the expression of miR-935 and Notch1 in gastric tissues. We conclude that miR-935 inhibits gastric carcinoma cell proliferation, migration and invasion by targeting Notch1, suggesting potential applications of the miR-935-Notch1 pathway in gastric cancer clinical diagnosis and therapeutics, especially in gastric signet ring cell carcinoma.
authors.affiliation: Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Yan
authors.affiliation: Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China. Electronic address: yu_jchpumch@163.com.
authors.forename: Jianchun
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China.
authors.forename: Weiming
authors.initials: W
authors.lastname: Kang
authors.affiliation: Cell Culture Center, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100005, China.
authors.forename: Yuqin
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
mesh_terms: D000328:Adult; D000368:Aged; D063646:Carcinogenesis / Q000378:metabolism* / Q000473:pathology*; D018279:Carcinoma, Signet Ring Cell / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology*
chemical_list: C000608148:MIRN-935 microRNA, human; D035683:MicroRNAs
keywords: Gastric signet-ring cell carcinoma (GSRCC); MiR-935; Notch1