Kindlin-2-mediated upregulation of ZEB2 facilitates migration and invasion of oral squamous cell carcinoma in a miR-200b-dependent manner
Authors: Cui Qiang
Xinjuan Kong
Keqian Zhi
Qibo Wang
Jingjing Zheng
Guangfeng Cai
Shaoming Li
Yuan Zhi
Zhigang Qu
Ling Gao
Minzhan Zhou
Wenhao Ren
Journal: American journal of translational research (2018)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Kindlin-2; OSCC; Oral squamous cell carcinoma; ZEB2; ceRNA
Affiliations: 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 Maxillofacial Surgery, College of Stomatology, Xi'an Jiaotong University Xi'an, Shaanxi, P. R. China., Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University Xi'an, Shaanxi, P. R. China., Department of Endodontics, The Affiliated Hospital of Qingdao University Qingdao, Shandong, P. R. China., Xiangya School of Stomatology, Central South University Changsha 410008, Hunan, P. R. China., Department of Oral and Maxillofacial Surgery, Shandong Jining No. 1 People's Hospital Jining, 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.

Abstract:  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. 

Retracted: No

PubPeer comments:
 In Figure 3F and 5D, micrographs have beed duplicated and presented in the same figure or in a different figure. In Figure 5E, a micrograph has been duplicated, rotated and presented as something else. ![file] , 
 #1 Dear Sir or Madam: Thank you for your inquiry. We have attached great importance to this matter and checked the original data as soon as possible when we received your comment on our paper. In the published version of Figure 3F and Figure 5D, the data in transwell assay and Figure 5E, the data for NC group and si-Dicer group in would healing assays, were inadvertently presented with incorrect images during figure assembly for manuscript submission. The data were not manipulated in any way, and the errors have no bearings on the interpretation of the results, nor do they influence the conclusions of the work. We are also contacting the Journal for correction and will update the status of the Journal correction here. Thanks again. ,