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

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.

journal_name

Am J Transl Res

authors

Ren W,Gao L,Qiang C,Li S,Zheng J,Wang Q,Zhi Y,Cai G,Kong X,Zhou M,Qu Z,Zhi K

subject

Has Abstract

pub_date

2018-08-15 00:00:00

pages

2529-2541

issue

8

issn

1943-8141

journal_volume

10

pub_type

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