Induction of epithelial-mesenchymal transition (EMT) by Beclin 1 knockdown via posttranscriptional upregulation of ZEB1 in thyroid cancer cells

// Si Li 1, * , Hai-Yan Zhang 2, * , Zhen-Xian Du 3 , Chao Li 1 , Ming-Xin An 1 , Zhi-Hong Zong 1 , Bao-Qin Liu 1 , Hua-Qin Wang 1 1 Department of Biochemistry and Molecular Biology, China Medical University, Shenyang 110001, China 2 Department of Geriatrics, the 1st Affiliated Hospital, China Medical University, Shenyang 110001, China 3 Department of Endocrinology and Metabolism, the 1st Affiliated Hospital, China Medical University, Shenyang 110001, China * These authors contributed equally to this work Correspondence to: Hua-Qin Wang, email: hqwang@cmu.edu.cn Keywords: Beclin1, EMT, invasion, thyroid cancer Received: May 02, 2016      Accepted: September 02, 2016      Published: September 23, 2016 ABSTRACT Beclin 1 has emerged as a haploinsufficient tumor suppression gene in a variety of human carcinomas. In order to clarify the role of Beclin 1 in thyroid cancer, Beclin 1 was knockdown in thyroid cancer cell lines. The current study demonstrated that knockdown of Beclin 1 resulted in morphological and molecular changes of thyroid cancer cells consistent with epithelial-mesenchymal transition (EMT), a morphogenetic procedure during which cells lose their epithelial characteristics and acquire mesenchymal properties concomitantly with gene expression reprogramming. In addition, the current study presented evidence demonstrating that Beclin 1 knockdown triggered this prometastatic process via stabilization of the EMT inducer ZEB1 mRNA through upregulation of AU-binding factor 1 (AUF1), which is recruited to the 3’-untranslated region (UTR) of the ZEB1 mRNA and decreases its degradation. We also found a negative correlation of Beclin 1 with AUF1 or ZEB1 in thyroid cancer tissues. These results indicated that at least some tumor suppressor functions of Beclin 1 were mediated through posttranscriptional regulation of ZEB1 via AUF1 in thyroid cancers.