Kindlin-2-mediated upregulation of ZEB2 facilitates migration and invasion of oral squamous cell carcinoma in a miR-200b-dependent manner

American Journal of Translational Research

Shaoming Li¹  Yuan Zhi²  Guangfeng Cai³  Ling Gao⁴  Wenhao Ren⁵  Qibo Wang⁶  Cui Qiang⁷  Jingjing Zheng⁸ 

[1] Department of Endodontics, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, P. R. China;Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, P. R. China;Department of Hand and Foot Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, P. R. China;Department of Oral Maxillofacial Surgery, College of Stomatology, Xian Jiaotong University, Xian, Shaanxi, P. R. China;Department of Oral Maxillofacial Surgery, Key Lab of Oral Clinical Medicine, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, P. R. China;Department of Oral and Maxillofacial Surgery, Shandong Jining No. 1 Peoples Hospital, Jining, Shandong, P. R. China;Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xian Jiaotong University, Xian, Shaanxi, P. R. China;Xiangya School of Stomatology, Central South University, Changsha 410008, Hunan, P. R. China

关键词: Oral squamous cell carcinoma;    OSCC;    ZEB2;    Kindlin-2;    miR-200b;    ceRNA;   

DOI  :  

学科分类：医学（综合）

来源: e-Century Publishing Corporation

【 摘 要 】

The miR-200 family suppresses epithelial-mesenchymal transition by inhibiting ZEB1 and ZEB2 mRNA translation in several types of cancers. Kindlin-2 is a target gene of miR-200b and its expression level correlates positively to ZEB2 in oral squamous cell carcinoma (OSCC). Whether Kindlin-2 and ZEB2 share a competitive endogenous RNAs regulatory network in OSCC remains unclear. Here, we studied the expression levels of miR-200b, Kindlin-2, and ZEB2 and found direct interaction between miR-200b, ZEB2, and Kindlin-2 mRNA in OSCC. A series of experiments was performed to elucidate the role of miR-200b and Kindlin-2 in OSCC cells. To further investigate whether Kindlin-2 regulates ZEB2 as a “ceRNA”, we utilized pools of siRNAs to deplete Kindlin-2 or ZEB2 in Tca-8113 cells. Significantly elevated expression levels of Kindlin-2 and ZEB2, down-regulated mRNA levels of miR-200b, and a positive correlation between Kindlin-2 and ZEB2 were found in OSCC cells. Additional results suggest that miR-200b directly targets ZEB2 and that Kindlin-2 3’UTR miR-200b repressed both the migration and invasive functionality of Tca-8113. Kindlin-2 and ZEB2 are involved in accelerated migration and invasion of Tca-113 cells in vitro and Kindlin-2 controlled ZEB2 expression. However, Kindlin-2-mediated ZEB2 regulation did not depend on miRNAs. These results indicate that Kindlin-2 does not act as ZEB2 ceRNA and modify the migration of Tca-8113 cells. Our results improve our understanding of the underlying molecular and cellular mechanisms of oral cancer metastasis.

【 授权许可】

CC BY-NC