title: SNORA74B gene silencing inhibits gallbladder cancer cells by inducing PHLPP and suppressing Akt/mTOR signaling.
abstract: Small nucleolar RNAs (snoRNAs) have been implicated in the development of many cancers. We therefore examined the differential expression of snoRNAs between gallbladder cancer (GBC) tissues and matched adjacent non-tumor tissues using expression microarray analysis with confirmation by quantitative real-time PCR (qRT-PCR). Western blot analysis showed that SNORA74B levels were higher in GBC than non-tumor tissues. SNORA74B expression was positively associated with local invasion, advanced TNM stage, CA19-9 level, and Ki67 expression in patients with GBC, while it was negatively associated with expression of PHLPP, an endogenous Akt inhibitor. Moreover, SNORA74B expression was prognostic for overall survival (OS) and disease-free survival (DFS). Functional studies revealed that silencing SNORA74B in GBC cells using sh-SNORA74B suppressed cell proliferation, induced G1 arrest, and promoted apoptosis. Preliminary molecular investigation revealed that SNORA74B silencing inhibited activation of the AKT/mTOR signaling pathway, while increasing PHLPP expression. PHLPP depletion using shRNA abrogated sh-SNORA74B suppression of GBC cell proliferation, indicating that the antitumor effects of SNORA74B silencing were mediated by PHLPP. These findings define the important role of SNORA74B in cell proliferation, cell cycle, and apoptosis of GBC, and suggest that it may serve as a novel target for GBC treatment.
authors.affiliation: Clinical College, Yancheng Institute of Health Sciences, Yancheng, Jiangsu 224000, China.|Research Centre of Biomedical Technology, Yancheng Institute of Health Sciences, Yancheng, Jiangsu 224000, China.|Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.|Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: Yiyu
authors.initials: Y
authors.lastname: Qin
authors.affiliation: Research Centre of Biomedical Technology, Yancheng Institute of Health Sciences, Yancheng, Jiangsu 224000, China.
authors.forename: Li
authors.initials: L
authors.lastname: Meng
authors.affiliation: Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Quan
authors.affiliation: Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors.forename: Mingzhe
authors.initials: M
authors.lastname: Ma
authors.affiliation: Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors.forename: Mingzhe
authors.initials: M
authors.lastname: Weng
authors.affiliation: Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: Zhengdong
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Research Centre of Biomedical Technology, Yancheng Institute of Health Sciences, Yancheng, Jiangsu 224000, China.
authors.forename: Cuixiang
authors.initials: C
authors.lastname: Gao
authors.affiliation: Research Centre of Biomedical Technology, Yancheng Institute of Health Sciences, Yancheng, Jiangsu 224000, China.
authors.forename: Xinghua
authors.initials: X
authors.lastname: Shi
authors.affiliation: Clinical College, Yancheng Institute of Health Sciences, Yancheng, Jiangsu 224000, China.
authors.forename: Koulan
authors.initials: K
authors.lastname: Han
mesh_terms: D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle; D049109:Cell Proliferation; D005260:Female; D005500:Follow-Up Studies; D005706:Gallbladder Neoplasms / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors*; D020537:RNA, Small Nucleolar / Q000037:antagonists & inhibitors* / Q000235:genetics; D015996:Survival Rate; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; D009687:Nuclear Proteins; D020537:RNA, Small Nucleolar; C546842:MTOR protein, human; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C400601:PHLPP1 protein, human; D010749:Phosphoprotein Phosphatases
keywords: AKT; PHLPP; SNORA74B; gallbladder cancer; snoRNA