Jun Liu1, Xionghui He2, Yongping Zou3, Kaiqiong Wang4. 1. Department of Hepatobiliary Pancreatic Surgery, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, No. 19, Xiuhua Road, Xiuying District, Haikou, Hainan, China. 2. Department of Gastrointestinal Surgery, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, 570311, Hainan, China. 3. Department of Emergency Surgery, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, 570311, Hainan, China. 4. Department of Hepatobiliary Pancreatic Surgery, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, No. 19, Xiuhua Road, Xiuying District, Haikou, Hainan, China. lcycid@163.com.
Abstract
BACKGROUND: Circular RNAs (circRNAs) are implicated in the pathogenesis and development of hepatocellular carcinoma (HCC). However, the function and latent mechanism of circ-STIL in HCC have not been elucidated. AIMS: This study was designed to explore the precise role and underlying molecular mechanism of circ-STIL in HCC advancement. METHODS: The expression levels of circ-STIL, SCL/TAL1 interrupting locus (STIL), miR-345-5p and aquaporin-3 (AQP3) were measured by quantitative real-time polymerase chain reaction or western blot. Cell proliferation was assessed by 3-(4,5-dimethylthizol-2-yl)-2,5-diphenyltetrazolium bromide assay and colony formation assay. Cell apoptosis was analyzed by flow cytometry. Transwell assay was conducted to analyze cell migratory and invasive capacities. The interactions among circ-STIL, miR-345-5p and AQP3 were confirmed by dual-luciferase reporter and RNA immunoprecipitation assays. Xenograft tumor model was established to analyze the role of circ-STIL in HCC in vivo. RESULTS: Circ-STIL was upregulated in HCC tissues and cells. Circ-STIL knockdown inhibited HCC cell progression by reducing cell proliferation, migration and invasion and promoting cell apoptosis. MiR-345-5p was a direct target of circ-STIL, and AQP3 was targeted by miR-345-5p in HCC. Circ-STIL knockdown or miR-345-5p overexpression impeded cell malignant behaviors in HCC cells, and the effects could be reversed by miR-345-5p silence or AQP3 enhancement, respectively. Meanwhile, circ-STIL regulated AQP3 expression by sponging miR-345-5p. Besides, circ-STIL downregulation retarded HCC tumor growth in vivo. CONCLUSION: Circ-STIL knockdown suppressed HCC development by regulating miR-345-5p/AQP3 pathway, which might provide a promising target for HCC therapy.
BACKGROUND: Circular RNAs (circRNAs) are implicated in the pathogenesis and development of hepatocellular carcinoma (HCC). However, the function and latent mechanism of circ-STIL in HCC have not been elucidated. AIMS: This study was designed to explore the precise role and underlying molecular mechanism of circ-STIL in HCC advancement. METHODS: The expression levels of circ-STIL, SCL/TAL1 interrupting locus (STIL), miR-345-5p and aquaporin-3 (AQP3) were measured by quantitative real-time polymerase chain reaction or western blot. Cell proliferation was assessed by 3-(4,5-dimethylthizol-2-yl)-2,5-diphenyltetrazolium bromide assay and colony formation assay. Cell apoptosis was analyzed by flow cytometry. Transwell assay was conducted to analyze cell migratory and invasive capacities. The interactions among circ-STIL, miR-345-5p and AQP3 were confirmed by dual-luciferase reporter and RNA immunoprecipitation assays. Xenograft tumor model was established to analyze the role of circ-STIL in HCC in vivo. RESULTS: Circ-STIL was upregulated in HCC tissues and cells. Circ-STIL knockdown inhibited HCC cell progression by reducing cell proliferation, migration and invasion and promoting cell apoptosis. MiR-345-5p was a direct target of circ-STIL, and AQP3 was targeted by miR-345-5p in HCC. Circ-STIL knockdown or miR-345-5p overexpression impeded cell malignant behaviors in HCC cells, and the effects could be reversed by miR-345-5p silence or AQP3 enhancement, respectively. Meanwhile, circ-STIL regulated AQP3 expression by sponging miR-345-5p. Besides, circ-STIL downregulation retarded HCC tumor growth in vivo. CONCLUSION: Circ-STIL knockdown suppressed HCC development by regulating miR-345-5p/AQP3 pathway, which might provide a promising target for HCC therapy.