Research Paper Volume 11, Issue 10 pp 3362—3375

Circular RNA hsa_circ_0001649 inhibits hepatocellular carcinoma progression via multiple miRNAs sponge

Yang Su 1, 2, *, , Chao Xu 1, *, , Yuting Liu 1, , Yilin Hu 3, , Haiyan Wu 1, ,

  • 1 Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University, Huaian, China
  • 2 State Key Laboratory of Reproductive Medicine, Center for Global Health, Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China
  • 3 Research Center of Clinical Medicine, Nantong University Affiliated Hospital, Nantong, China
* Equal contribution

received: December 16, 2018 ; accepted: May 20, 2019 ; published: May 28, 2019 ;

https://doi.org/10.18632/aging.101988
How to Cite

Copyright: Su et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Circular RNA (circRNA) exerts an essential role in tumor development. Hsa_circ_0001649 (circ-0001649) was produced at the SHPRH gene locus containing exon 26-29. This study analyzed the specific mechanism of circ-0001649 in influencing the development of hepatocellular carcinoma (HCC). Relative levels of circ-0001649 in HCC cell lines and tissues were examined by qRT-PCR. The direct binding between circ-0001649 and miR-127-5p/miR-612/miR-4688 were verified through Dual-luciferase reporter gene assay, RNA Binding Protein Immunoprecipitation (RIP) assay and western blot detection. In vitro and in vivo regulatory roles of circ-0001649 in proliferative and migratory abilities of HCC were evaluated by EdU, Transwell and tumourigenicity assay, respectively. Results showed that circ-0001649 was markedly decreased in hepatocellular carcinoma cell lines and tumor tissues. Overexpression of circ-0001649 greatly inhibited proliferation and migration of HCC in vitro and in vivo. More importantly, we confirmed that circ-0001649 regulated cellular behaviors of HCC cells by targeting SHPRH. Furthermore, we determined that circ-0001649 served as a ceRNA to sponge miR-127-5p, miR-612 and miR-4688, thus activating SHPRH. In summary, our study showed that circ-0001649 was lowly expressed in HCC and inhibited HCC progression via multiple miRNAs sponge.

Abbreviations

HCC: hepatocellular carcinoma; SHPRH: SNF2 histone linker PHD RING helicase; EdU: 5-ethynyl-2'-deoxyuridine; ceRNA: competing endogenous RNAs; circRNA: Circular RNA; RIP: RNA Binding Protein Immunoprecipitation; AUC: area under the ROC curve; DMEM: Dulbecco’s Modified Eagle medium; SDS-PAGE: sodium dodecyl sulphate-polyacrylamide gel electrophoresis.