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

被引:14
|
作者
Sun, Chengjun [1 ,2 ,3 ]
Huang, Shanzhou [4 ]
Hou, Yuchen [5 ]
Li, Zhongqiu [1 ]
Xia, Dongmei [8 ]
Zhang, Lishan [1 ]
Zhang, Yixi [1 ,2 ,3 ]
Cai, Yifeng [8 ]
Wang, Ziming [6 ]
Zhou, Qi [7 ,8 ]
He, Xiaoshun [1 ,2 ,3 ]
Wu, Linwei [1 ,2 ,3 ]
机构
[1] Sun Yat Sen Univ, Affiliated Hosp 1, Organ Transplant Ctr, Guangzhou 510080, Peoples R China
[2] Guangdong Prov Key Lab Organ Donat & Transplant I, Guangzhou 510080, Peoples R China
[3] Guangdong Prov Int Cooperat Base Sci & Technol, Guangzhou 510080, Peoples R China
[4] South China Univ Technol, Guangdong Acad Med Sci, Sch Med, Dept Gen Surg,Guangdong Gen Hosp, Guangzhou 510080, Peoples R China
[5] Shanghai Jiao Tong Univ, Ren Ji Hosp, Sch Med, Dept Liver Surg, Shanghai 200127, Peoples R China
[6] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Biliary & Pancreat Surg, Guangzhou 510080, Peoples R China
[7] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Liver Surg, Guangzhou 510080, Peoples R China
[8] Sun Yat Sen Univ, Hui Ya Hosp, Affiliated Hosp 1, Dept Gen Surg, Huizhou 516081, Guangdong, Peoples R China
来源
AGING-US | 2020年 / 12卷 / 14期
基金
中国国家自然科学基金;
关键词
cancer; hepatocellular carcinoma; AC092171.4; epithelial-to-mesenchymal transition; survival;
D O I
10.18632/aging.103419
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:14141 / 14156
页数:16
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