Research Paper Advance Articles

Long noncoding RNA AC092171.4 promotes hepatocellular carcinoma progression by sponging microRNA-1271 and upregulating GRB2

Chengjun Sun1,2,3, *, , Shanzhou Huang4, *, , Yuchen Hou5, *, , Zhongqiu Li1, , Dongmei Xia8, , Lishan Zhang1, , Yixi Zhang1,2,3, , Yifeng Cai8, , Ziming Wang6, , Qi Zhou7,8, , Xiaoshun He1,2,3, , Linwei Wu1,2,3, ,

  • 1 Organ Transplant Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China
  • 2 Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou 510080, China
  • 3 Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou 510080, China
  • 4 Department of General Surgery, Guangdong General Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou 510080, China
  • 5 Department of Liver Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
  • 6 Department of Biliary and Pancreatic Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China
  • 7 Department of Liver Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China
  • 8 Department of General Surgery, Hui Ya Hospital, The First Affiliated Hospital, Sun Yat-Sen University, Huizhou 516081, Guangdong, China
* Equal contribution and Co-first authors

Received: August 8, 2019       Accepted: May 19, 2020       Published: July 21, 2020      

https://doi.org/10.18632/aging.103419
How to Cite

Copyright © 2020 Sun 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

In this study, we investigated the mechanistic role of the long non-coding RNA (lncRNA) AC092171.4 in hepatocellular carcinoma (HCC). AC092171.4 was significantly upregulated in HCC tumor tissues compared to normal liver tissues. HCC patients with high AC092171.4 expression showed poorer overall survival (OS) and disease-free survival (DFS) than those with low AC092171.4 expression. In vitro cell proliferation, migration and invasiveness were all higher in AC092171.4-overexpressing HCC cells, but lower in AC092171.4-silenced HCC cells, than in controls. Balb/c nude mice injected with AC092171.4-silenced HCC cells had smaller xenograft tumors, which showed less growth and pulmonary metastasis than control tumors. Bioinformatics analyses and dual luciferase reporter assays confirmed that AC092171.4 binds directly to miR-1271, which targets the 3’UTR of GRB2 mRNA. AC092171.4 expression correlates negatively with miR1271 expression and correlates positively with GRB2 mRNA expression in HCC tissues from patients. HCC cells co-transfected with miR-1271 mimics and sh-AC092171.4 show less proliferation, migration, invasiveness, GRB2 protein, and epithelial to mesencyhmal transition (EMT) than sh-AC092171.4-transfected HCC cells. These findings demonstrate that AC092171.4 promotes growth and progression of HCC by sponging miR-1271 and upregulating GRB2. This makes AC092171.4 a potential prognostic indicator and therapeutic target for HCC patients.

Abbreviations

HCC: hepatocellular carcinoma; LncRNA: long noncoding RNA; ANLTs: adjacent normal liver tissues; GEPIA: gene expression profiling interactive analysis; FC: fold change; OS: overall survival; DFS: disease-free survival; qRT-PCR: quantitative real-time polymerase chain reaction; CISH: chromogenic in situ hybridization; ceRNA: competing endogenous RNA; IHC: immunohistochemistry; CCK8: cell counting kit-8; GRB2: growth factor receptor-bound 2; EMT: epithelial-to-mesenchymal transition; SD: standard deviation.