title: SSRP1 Contributes to the Malignancy of Hepatocellular Carcinoma and Is Negatively Regulated by miR-497.
abstract: The aim of this study is to clarify the clinical implication and functional role of structure specific recognition protein 1 (SSRP1) in hepatocellular carcinoma (HCC) and explore the underlying mechanism of aberrant high expression of SSRP1 in cancers. In the present investigation, we validated that SSRP1 was upregulated in HCC samples. We also demonstrated that its upregulation was associated with several clinicopathologic features such as higher serum AFP level, larger tumor size, and higher T stage of HCC patients; and its high expression indicated shorter overall survival and faster recurrence. To investigate the role of SSRP1 in HCC progression, both loss- and gain-function models were established. We demonstrated that SSPR1 modulated both proliferation and metastasis of HCC cells in vitro and vivo. Furthermore, we demonstrated that SSRP1-modulated apoptosis process and its knockdown increased the sensitivity of HCC cells to doxorubicin, 5-Fluorouracil, and cisplatin. We also identified microRNA-497 (miR-497) as a posttranscriptional regulator of SSRP1. Ectopic expression of miR-497 inhibited 3'-untranslated-region-coupled luciferase activity and suppressed endogenous SSRP1 expression at both messenger RNA and protein levels. For the first time, we proved that SSRP1 upregulation contributed to HCC development and the tumor-suppressive miR-497 served as its negative regulator.
authors.affiliation: Department of General Surgery, The Second People's Hospital of Guangdong Province, The 3rd Clinical Medicine School, Southern Medical University, Guangzhou, China.|Department of Gastroenterology, Institute for Gastroenterology and Hepatology, Renmin Hospital of Wuhan University, Wuhan, China.
authors.forename: Qianshan
authors.initials: Q
authors.lastname: Ding
authors.affiliation: Department of General Surgery, The Second People's Hospital of Guangdong Province, The 3rd Clinical Medicine School, Southern Medical University, Guangzhou, China.
authors.forename: Ke
authors.initials: K
authors.lastname: He
authors.affiliation: Department of Anatomy and Neurobiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Luo
authors.affiliation: Department of Gastroenterology, Institute for Gastroenterology and Hepatology, Renmin Hospital of Wuhan University, Wuhan, China.
authors.forename: Yunchao
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Department of General Surgery, The Second People's Hospital of Guangdong Province, The 3rd Clinical Medicine School, Southern Medical University, Guangzhou, China.
authors.forename: Hanning
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Vascular Surgery, Southern Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of General Surgery, The Second People's Hospital of Guangdong Province, The 3rd Clinical Medicine School, Southern Medical University, Guangzhou, China.
authors.forename: Jinqian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, The Second People's Hospital of Guangdong Province, The 3rd Clinical Medicine School, Southern Medical University, Guangzhou, China.
authors.forename: Kaiyun
authors.initials: K
authors.lastname: Chen
authors.affiliation: Department of General Surgery, The Second People's Hospital of Guangdong Province, The 3rd Clinical Medicine School, Southern Medical University, Guangzhou, China.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Xiao
authors.affiliation: Department of General Surgery, The Second People's Hospital of Guangdong Province, The 3rd Clinical Medicine School, Southern Medical University, Guangzhou, China.
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Duan
authors.affiliation: Department of General Surgery, The Second People's Hospital of Guangdong Province, The 3rd Clinical Medicine School, Southern Medical University, Guangzhou, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Huang
authors.affiliation: Department of General Surgery, The Second People's Hospital of Guangdong Province, The 3rd Clinical Medicine School, Southern Medical University, Guangzhou, China.
authors.forename: Zhenglin
authors.initials: Z
authors.lastname: Xia
authors.affiliation: Department of General Surgery, The Second People's Hospital of Guangdong Province, The 3rd Clinical Medicine School, Southern Medical University, Guangzhou, China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Department of General Surgery, The Second People's Hospital of Guangdong Province, The 3rd Clinical Medicine School, Southern Medical University, Guangzhou, China.
authors.forename: Jinliang
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Gastroenterology, Institute for Gastroenterology and Hepatology, Renmin Hospital of Wuhan University, Wuhan, China.
authors.forename: Honggang
authors.initials: H
authors.lastname: Yu
authors.affiliation: Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Xingyuan
authors.initials: X
authors.lastname: Jiao
authors.affiliation: Department of General Surgery, The Second People's Hospital of Guangdong Province, The 3rd Clinical Medicine School, Southern Medical University, Guangzhou, China.
authors.forename: Guoan
authors.initials: G
authors.lastname: Xiang
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006609:High Mobility Group Proteins / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D009367:Neoplasm Staging; D009368:Neoplasm Transplantation; D035602:Transcriptional Elongation Factors / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D020413:3' Untranslated Regions; D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; C559640:MIRN497 microRNA, human; D035683:MicroRNAs; C073537:SSRP1 protein, human; D035602:Transcriptional Elongation Factors