Zhibin Liao1,2, Hongwei Zhang1,2, Chen Su1,2, Furong Liu1,2, Yachong Liu1,2, Jia Song1,2, He Zhu1,2, Yawei Fan1,2, Xuewu Zhang1,2, Wei Dong1,2, Xiaoping Chen1,2,3,4, Huifang Liang5,6, Bixiang Zhang7,8,9,10. 1. Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P. R. China. 2. Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Wuhan, Hubei, P. R. China. 3. Key Laboratory of Organ Transplantation, Ministry of Education, Wuhan, Hubei, P. R. China. 4. Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, Hubei, P. R. China. 5. Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P. R. China. lianghuifang1997@126.com. 6. Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Wuhan, Hubei, P. R. China. lianghuifang1997@126.com. 7. Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P. R. China. bixiangzhang@163.com. 8. Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Wuhan, Hubei, P. R. China. bixiangzhang@163.com. 9. Key Laboratory of Organ Transplantation, Ministry of Education, Wuhan, Hubei, P. R. China. bixiangzhang@163.com. 10. Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, Hubei, P. R. China. bixiangzhang@163.com.
Abstract
BACKGROUND: Aberrant expressions of long noncoding RNAs (lncRNAs) have been demonstrated to be related to the progress of HCC. The mechanisms that SNHG14 has participated in the development of HCC are obscure. METHODS: Quantitative real-time PCR (qRT-PCR) was used to measure the lncRNA, microRNA and mRNA expression level. Cell migration, invasion and proliferation ability were evaluated by transwell and CCK8 assays. The ceRNA regulatory mechanism of SNHG14 was evaluated by RNA immunoprecipitation (RIP) and dual luciferase reporter assay. Tumorigenesis mouse model was used to explore the roles of miR-876-5p in vivo. The protein levels of SSR2 were measured by western blot assay. RESULTS: In this study, we demonstrated that SNHG14 was highly expressed in HCC tissues, meanwhile, the elevated expression of SNHG14 predicted poor prognosis in patients with HCC. SNHG14 promoted proliferation and metastasis of HCC cells. We further revealed that SNHG14 functioned as a competing endogenous RNA (ceRNA) for miR-876-5p and that SSR2 was a downstream target of miR-876-5p in HCC. Transwell, CCK8 and animal experiments exhibited miR-876-5p inhibited HCC progression in vitro and in vivo. By conducting rescue experiments, we found the overexpression of SSR2 or knocking down the level of miR-876-5p could reverse the suppressive roles of SNHG14 depletion in HCC. CONCLUSION: SNHG14 promotes HCC progress by acting as a sponge of miR-876-5p to regulate the expression of SSR2 in HCC.
BACKGROUND: Aberrant expressions of long noncoding RNAs (lncRNAs) have been demonstrated to be related to the progress of HCC. The mechanisms that SNHG14 has participated in the development of HCC are obscure. METHODS: Quantitative real-time PCR (qRT-PCR) was used to measure the lncRNA, microRNA and mRNA expression level. Cell migration, invasion and proliferation ability were evaluated by transwell and CCK8 assays. The ceRNA regulatory mechanism of SNHG14 was evaluated by RNA immunoprecipitation (RIP) and dual luciferase reporter assay. Tumorigenesis mouse model was used to explore the roles of miR-876-5p in vivo. The protein levels of SSR2 were measured by western blot assay. RESULTS: In this study, we demonstrated that SNHG14 was highly expressed in HCC tissues, meanwhile, the elevated expression of SNHG14 predicted poor prognosis in patients with HCC. SNHG14 promoted proliferation and metastasis of HCC cells. We further revealed that SNHG14 functioned as a competing endogenous RNA (ceRNA) for miR-876-5p and that SSR2 was a downstream target of miR-876-5p in HCC. Transwell, CCK8 and animal experiments exhibited miR-876-5p inhibited HCC progression in vitro and in vivo. By conducting rescue experiments, we found the overexpression of SSR2 or knocking down the level of miR-876-5p could reverse the suppressive roles of SNHG14 depletion in HCC. CONCLUSION:SNHG14 promotes HCC progress by acting as a sponge of miR-876-5p to regulate the expression of SSR2 in HCC.
Authors: Hyun Jung Park; Ping Ji; Soyeon Kim; Zheng Xia; Benjamin Rodriguez; Lei Li; Jianzhong Su; Kaifu Chen; Chioniso P Masamha; David Baillat; Camila R Fontes-Garfias; Ann-Bin Shyu; Joel R Neilson; Eric J Wagner; Wei Li Journal: Nat Genet Date: 2018-05-21 Impact factor: 38.330