Induction of epithelial-mesenchymal transition (EMT) by Beclin 1 knockdown via posttranscriptional upregulation of ZEB1 in thyroid cancer cells.
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.
Department of Biochemistry and Molecular Biology, China Medical University, Shenyang 110001, China.
Si
S
Li
Department of Geriatrics, the 1st Affiliated Hospital, China Medical University, Shenyang 110001, China.
Hai-Yan
HY
Zhang
Department of Endocrinology and Metabolism, the 1st Affiliated Hospital, China Medical University, Shenyang 110001, China.
Zhen-Xian
ZX
Du
Department of Biochemistry and Molecular Biology, China Medical University, Shenyang 110001, China.
Chao
C
Li
Department of Biochemistry and Molecular Biology, China Medical University, Shenyang 110001, China.
Ming-Xin
MX
An
Department of Biochemistry and Molecular Biology, China Medical University, Shenyang 110001, China.
Zhi-Hong
ZH
Zong
Department of Biochemistry and Molecular Biology, China Medical University, Shenyang 110001, China.
Bao-Qin
BQ
Liu
Department of Biochemistry and Molecular Biology, China Medical University, Shenyang 110001, China.
Hua-Qin
HQ
Wang
D000071186:Beclin-1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D / Q000502:physiology; D006801:Humans; D013964:Thyroid Neoplasms / Q000473:pathology*; D025521:Tumor Suppressor Proteins / Q000502:physiology; D015854:Up-Regulation; D000071799:Zinc Finger E-box-Binding Homeobox 1 / Q000235:genetics*
D000071186:Beclin-1; C000630986:HNRNPD protein, human; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D; D025521:Tumor Suppressor Proteins; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1
Beclin1; EMT; invasion; thyroid cancer
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