TY - JOUR
T1 - Long noncoding RNA AC092171.4 promotes hepatocellular carcinoma progression by sponging microRNA-1271 and upregulating GRB2
AU - Sun, Chengjun
AU - Huang, Shanzhou
AU - Hou, Yuchen
AU - Li, Zhongqiu
AU - Xia, Dongmei
AU - Zhang, Lishan
AU - Zhang, Yixi
AU - Cai, Yifeng
AU - Wang, Ziming
AU - Zhou, Qi
AU - He, Xiaoshun
AU - Wu, Linwei
N1 - Funding Information:
This study was funded by the National Natural Science Foundation of China (Grant No. 81670592), Natural Science Foundation of Guangdong Province (Grant No. 2016A030313242), Guangdong Provincial Key Laboratory Construction Projection on Organ Donation and Transplant Immunology (Grant Nos. 2013A061401007 and 2017B030314018), Medical Scientific Research Foundation of Guangdong Province (Grant No. A2016033); Science and Technology Program of Guangzhou (Grant No. 201804020075), Fundamental Research Funds for the Central Universities (Grant Nos. 17ykjc09, 19ykzd14); Science and Technology Program of Huizhou (Grant Nos. 170520181743174, 180529101741637 and 2019C0602009), Ke Lin Program Foundation for Youth Talents (Grant No. y50181), Special Support Program for Training High Level Talents in Guangdong Province (Grant No. 2015TQ01R168), and Science and Technology Program of Guangzhou (Grant No. 201704020150). Special Funding for PhD doctor of Guangdong Provincial People's Hospital (2020bq09). Funding for the Construction of Key Specialty in Huizhou (Qi Zhou).
Publisher Copyright:
© Sun et al.
PY - 2020/7/21
Y1 - 2020/7/21
N2 - 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.
AB - 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.
KW - AC092171.4
KW - Cancer
KW - Epithelial-to-mesenchymal transition
KW - Hepatocellular carcinoma
KW - Survival
UR - http://www.scopus.com/inward/record.url?scp=85088844594&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85088844594&partnerID=8YFLogxK
U2 - 10.18632/aging.103419
DO - 10.18632/aging.103419
M3 - Article
C2 - 32692718
AN - SCOPUS:85088844594
SN - 1945-4589
VL - 12
SP - 14141
EP - 14156
JO - Aging
JF - Aging
IS - 14
ER -