Research Paper|Volume 12, Issue 14|pp 14141—14156

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

Chengjun Sun^1,^2,³, Shanzhou Huang⁴, Yuchen Hou⁵, Zhongqiu Li¹, Dongmei Xia⁸, Lishan Zhang¹, Yixi Zhang^1,^2,³, Yifeng Cai⁸, Ziming Wang⁶, Qi Zhou^7,⁸, Xiaoshun He^1,^2,³, Linwei Wu^1,^2,³

¹Organ Transplant Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China
²Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou 510080, China
³Guangdong Provincial International Cooperation Base of Science and Technology, Guangzhou 510080, China
⁴Department of General Surgery, Guangdong General Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou 510080, China
⁵Department of Liver Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
⁶Department of Biliary and Pancreatic Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China
⁷Department of Liver Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China
⁸Department 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, 2019Accepted: May 19, 2020Published: July 21, 2020

https://doi.org/10.18632/aging.103419

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.