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

// Rui Gao 1,* , Chunli Cai 1,* , Jiancheng Gan 2,* , Xi Yang 1 , Zeyu Shuang 3 , Min Liu 1 , Shengping Li 3 and Hua Tang 1 1 Tianjin Life Science Research Center and Basic Medical School, Tianjin Medical University, Tianjin, China 2 Department of Surgery, Secondary Hospital of Tianjin Medical University, Tianjin, China 3 State Key Laboratory of Oncology in Southern China, Department of Hepatobiliary Oncology, Cancer Center, Sun Yat-sen University, Guangzhou, China * These authors contributed equally to this work Correspondence to: Hua Tang, email: // Shengping Li, email: // Keywords : microRNA; microRNA-1236; AFP; PTEN; hepatocellular cancer Received : November 09, 2014 Accepted : January 14, 2015 Published : January 21, 2015 Abstract 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.