title: Upregulation of SNHG6 regulates ZEB1 expression by competitively binding miR-101-3p and interacting with UPF1 in hepatocellular carcinoma.
abstract: Emerging evidence suggests that small nucleolar RNAs (snoRNAs) and their host genes (SNHGs) have malfunctioning roles in the development of human cancers. We globally investigated the molecular mechanisms by which snoRNA host gene 6 (SNHG6) promotes hepatocellular carcinoma (HCC) progression using human tissues and cell lines. We found that SNHG6 is overexpressed in HCC tissues and in hepatoma cell lines and is closely associated with histologic grade, hepatitis B virus DNA, Barcelona Clinic Liver Cancer stage and portal vein tumor thrombus in patients with HCC. Knockdown of SNHG6 induced apoptosis and repressed cell cycle progression in hepatoma cell lines, whereas transgenic expression of SNHG6 in the immortalized human hepatic cell line L02 had opposite effects. Xenograft tumors grown from SNHG6-knockdown cells had smaller mean volumes than did tumors grown from control cells. SNHG6 may act as a competing endogenous RNA, effectively becoming a sink for miR-101-3p and thereby modulating the derepression of zinc finger E-box binding homeobox 1, imposing an additional level of post-transcriptional regulation. Functionally, SNHG6 promotes tumor growth and metastasis by inducing epithelial to mesenchymal transition. Further investigations showed that SNHG6 could affect HCC tumorigenesis by binding to up-frameshift protein 1 and regulating Smad7 expression.
authors.affiliation: Department of General Surgery, Research Center of Digestive Diseases, Zhongnan Hospital of Wuhan University, Wuhan, 430071, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Chang
authors.affiliation: Department of General Surgery, Research Center of Digestive Diseases, Zhongnan Hospital of Wuhan University, Wuhan, 430071, PR China.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan, 430071, PR China.
authors.forename: Cuicui
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of General Surgery, Research Center of Digestive Diseases, Zhongnan Hospital of Wuhan University, Wuhan, 430071, PR China.
authors.forename: Tao
authors.initials: T
authors.lastname: Guo
authors.affiliation: Department of General Surgery, Research Center of Digestive Diseases, Zhongnan Hospital of Wuhan University, Wuhan, 430071, PR China.
authors.forename: Haolong
authors.initials: H
authors.lastname: Qi
authors.affiliation: Department of General Surgery, Research Center of Digestive Diseases, Zhongnan Hospital of Wuhan University, Wuhan, 430071, PR China.
authors.forename: Yusha
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Hainan Provincial Key Laboratory of Carcinogenesis and Intervention, Hainan Medical College, Haikou, Hainan, 571199, PR China.
authors.forename: Xu
authors.initials: X
authors.lastname: Dong
authors.affiliation: Department of General Surgery, Research Center of Digestive Diseases, Zhongnan Hospital of Wuhan University, Wuhan, 430071, PR China. Electronic address: spss2005@126.com.
authors.forename: Zhisu
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of General Surgery, Research Center of Digestive Diseases, Zhongnan Hospital of Wuhan University, Wuhan, 430071, PR China. Electronic address: lqy@whu.edu.cn.
authors.forename: Quanyan
authors.initials: Q
authors.lastname: Liu
mesh_terms: D000368:Aged; D000818:Animals; D017209:Apoptosis; D001667:Binding, Competitive; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle; D002465:Cell Movement; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D020365:RNA Helicases; D034622:RNA Interference; D020537:RNA, Small Nucleolar / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D051906:Smad7 Protein / Q000378:metabolism; D013997:Time Factors; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000378:metabolism; D000071799:Zinc Finger E-box-Binding Homeobox 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: C534072:MIRN101 microRNA, human; D035683:MicroRNAs; D020537:RNA, Small Nucleolar; C497806:SMAD7 protein, human; D051906:Smad7 Protein; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; D020365:RNA Helicases; C101828:UPF1 protein, human
keywords: EMT; Hepatocellular carcinoma; UPF1; ZEB1; snoRNA host gene 6 (SNHG6)