MicroRNA-26a promotes anoikis in human hepatocellular carcinoma cells by targeting alpha5 integrin

// Xiang Zhang 1,* , Shu-Li Cheng 2,* , Ka Bian 3,4,* , Lei Wang 1 , Xiao Zhang 1 , Bo Yan 1 , Lin-Tao Jia 1 , Jing Zhao 1 , Noor Gammoh 5 , An-Gang Yang 4 and Rui Zhang 1 1 State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, the Fourth Military Medical University, Xi’an, Shaanxi, China 2 Department of Orthodontics, School of Stomatology, the Fourth Military Medical University, Xi’an Shaanxi, China 3 Department of Otolaryngology, Tangdu Hospital, the Fourth Military Medical University, Xi’an Shaanxi, China 4 State Key Laboratory of Cancer Biology, Department of Immunology, the Fourth Military Medical University, Xi’an, Shaanxi, China 5 Edinburgh Cancer Research Centre, The University of Edinburgh, Western General Hospital, Edinburgh EH4 2XR, United Kingdom * These authors contributed equally to this work Correspondence: Rui Zhang, email: // An-Gang Yang, email: // Keywords : microRNA-26a, ITGA5, human hepatocellular carcinoma, anoikis, tumor metastasis Received : October 13, 2014 Accepted : December 09, 2014 Published : December 10, 2014 Abstract Metastasis is the major reason for the death of patients suffering from malignant diseases such as human hepatocellular carcinoma (HCC). Among the complex metastatic process, resistance to anoikis is one of the most important steps. Previous studies demonstrate that microRNA-26a (miR-26a) is an important tumor suppressor that inhibits the proliferation and invasion of HCC cells by targeting multiple oncogenic proteins. However, whether miR-26a can also influence anoikis has not been well established. Here, we discovered that miR-26a promotes anoikis of HCC cells both in vitro and in vivo. With a combinational analysis of bioinformatics and public clinical databases, we predicted that alpha5 integrin (ITGA5), an integrin family member, is a putative target of miR-26a. Furthermore, we provide experimental evidence to confirm that ITGA5 is a bona fide target of miR-26a. Through gain- and loss-of-function studies, we demonstrate that ITGA5 is a functional target of miR-26a-induced anoikis in HCC cells. Collectively, our findings reveal that miR-26a is a novel player during anoikis and a potential therapeutic target for the treatment of metastatic HCC.