miR-1236 down-regulates alpha-fetoprotein, thus causing PTEN accumulation, which inhibits the PI3K/Akt pathway and malignant phenotype in hepatoma cells

被引:65
作者
Gao, Rui [1 ,2 ]
Cai, Chunli [1 ,2 ]
Gan, Jiancheng [3 ]
Yang, Xi [1 ,2 ]
Shuang, Zeyu [4 ]
Liu, Min [1 ,2 ]
Li, Shengping [4 ]
Tang, Hua [1 ,2 ]
机构
[1] Tianjin Med Univ, Tianjin Life Sci Res Ctr, Tianjin, Peoples R China
[2] Tianjin Med Univ, Basic Med Sch, Tianjin, Peoples R China
[3] Tianjin Med Univ, Dept Surg, Secondary Hosp, Tianjin, Peoples R China
[4] Sun Yat Sen Univ, Dept Hepatobiliary Oncol, Ctr Canc, State Key Lab Oncol Southern China, Guangzhou 510275, Guangdong, Peoples R China
基金
中国国家自然科学基金;
关键词
microRNA; microRNA-1236; AFP; PTEN; hepatocellular cancer; HUMAN HEPATOCELLULAR-CARCINOMA; X-LINKED INHIBITOR; SIGNALING PATHWAY; MESENCHYMAL TRANSITION; LIVER-CANCER; GENE; TARGETS; PROLIFERATION; PROGNOSIS; MARKER;
D O I
10.18632/oncotarget.3338
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
Alpha fetoprotein (AFP) is a clinical biomarker of hepatocellular carcinoma (HCC). Here, we found that miR-1236 is down-regulated, whereas AFP is highly expressed in HCC tissues and cells. We demonstrated that miR-1236 directly targets the 3'UTR of AFP and down-regulates its expression. Also, miR-1236 inhibited and AFP stimulated proliferation, migration, invasion and vasculogenic mimicry (VM) of HCC. In agreement, AFP over-expression counteracted the inhibitory effect of miR-1236. We demonstrated that AFP promoted the ubiquitination of PTEN, thus decreasing PTEN levels, while miR-1236 inhibited the PI3K/Akt pathway.
引用
收藏
页码:6014 / 6028
页数:15
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