title: SND1 affects proliferation of hepatocellular carcinoma cell line SMMC-7721 by regulating IGFBP3 expression.
abstract: Staphylococcal nuclease domain containing 1 (SND1) is a ubiquitously expressed multifunctional protein involved in transcriptional regulation, RNA splicing and RNA metabolism. Ectopic expression of SND1 has been observed in various tumors including colon cancer, breast cancer, prostate cancer and hepatocellular carcinoma (HCC), indicating a positive role of SND1 in tumor initiation and progression. However, the exact role of SND1 in cancers has not been thoroughly investigated. In the present study, we investigated the role of SND1 in HCC. Immunohistochemistry analysis revealed that the expression level of SND1 was higher in HCC tissues than in adjacent nontumor tissues. Stable knock-down of SND1, performed on the HCC cell line SMMC-7721 using shRNA lentiviral expression system, led to reduced cell proliferation, clone formation and tumor formation in nude mice. The insulin-like growth factor (IGF) signaling pathway was frequently dysregulated in HCC, which could facilitate tumor progression. Screening of gene expression levels of the IGF pathway, using real-time PCR, revealed that a decrease in SND1 expression could increase the expression of IGF-binding protein 3 (IGFBP3), which can negatively regulate activation of the IGF pathway by restricting interactions between IGF and IGF receptors. Results from previous studies showed that the downregulation of IGFBP3 expression is a common feature in HCC, and the upregulation of IGFBP3 expression could suppress HCC cells proliferation. We further confirmed that stable knock-down of IGFBP3 could promote SMMC-7721 cells proliferation. Therefore, we concluded that SND1 could affect SMMC-7721 cells proliferation by regulating IGFBP3 expression and IGF signaling pathway.
authors.affiliation: Department of Immunology and Biochemistry, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, People's Republic of China; Tianjin Key Laboratory of Cellular and Molecular Immunology, Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin, People's Republic of China; Key laboratory of Educational Ministry of China, Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin, People's Republic of China; Laboratory of Molecular Immunology, Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin, People's Republic of China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yin
authors.forename: Jianmin
authors.initials: J
authors.lastname: Ding
authors.forename: Li
authors.initials: L
authors.lastname: Huang
authors.forename: Xiao
authors.initials: X
authors.lastname: Tian
authors.forename: Xuebin
authors.initials: X
authors.lastname: Shi
authors.forename: Lei
authors.initials: L
authors.lastname: Zhi
authors.forename: Juan
authors.initials: J
authors.lastname: Song
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xingjie
authors.initials: X
authors.lastname: Gao
authors.forename: Zhi
authors.initials: Z
authors.lastname: Yao
authors.forename: Xiang
authors.initials: X
authors.lastname: Jing
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D004720:Endonucleases; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D009687:Nuclear Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D004720:Endonucleases; C095221:SND1 protein, human
keywords: IGF pathway; IGFBP3; SMMC-7721; SND1; cell proliferation; hepatocellular carcinoma