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Copyright (c) 2023 Wenwen Liu, Lihui Fan, Bo Shao, Yang Zhang
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
The undersigned hereby assign all rights, included but not limited to copyright, for this manuscript to CMB Association upon its submission for consideration to publication on Cellular and Molecular Biology. The rights assigned include, but are not limited to, the sole and exclusive rights to license, sell, subsequently assign, derive, distribute, display and reproduce this manuscript, in whole or in part, in any format, electronic or otherwise, including those in existence at the time this agreement was signed. The authors hereby warrant that they have not granted or assigned, and shall not grant or assign, the aforementioned rights to any other person, firm, organization, or other entity. All rights are automatically restored to authors if this manuscript is not accepted for publication.STAT3 promotes migration and invasion of cholangiocarcinoma arising from choledochal cyst by transcriptionally inhibiting miR200c through the c-myb/MEK/ERK signaling pathway
Corresponding Author(s) : Yang Zhang
Cellular and Molecular Biology,
Vol. 69 No. 9: Issue 9
Abstract
Signal transducer and activator of transcription 3 (STAT3) have been highlighted in cancer regulation. Its roles in Cholangiocarcinoma (CCA) arising from the choledochal cyst (CC) were unclear. Here, we attempted to elucidate the roles of STAT3 in CCA-CC and explore its mechanism. A total of 20 patients with CCA arising from CC, that underwent CC excision in the infant stage were included. The expressions of STAT3, miR200c and c-Myb in clinical samples were assessed by RT-qPCR and/or western blot. Their expression correlations in tumor tissues were evaluated by Pearson correlation analysis. Their roles in CCA cell migration and invasion were investigated by gene silence using siRNA or miRNA inhibitor mediated approach and MEK activator. The expression levels of EMT, metastasis and MEK/ERK pathway-related proteins were checked by western blot. The high expressions of STAT3 and c-Myb, and low expression of miR200c were detected in CCA samples. We defined the transcription inhibition of STAT3 in miR200c expression and the negative correlation between miR200c and c-Myb expression. Silence of STAT3 increased miR200c expression and retarded the migration and invasion of CCA cells, accompanied by decreased levels of Vimentin, N-cadherin, MMP2 and MMP9, and elevated expression of E-cadherin, resulting in inactivating MEK/ERK pathway. MiR200c inhibitor reversed the changes induced by STAT3 silence, which was restored by si-c-Myb. MEK activator significantly reversed the inactivation of the MEK/ERK pathway induced by si-STAT3+miR200c inhibitor+si-c-Myb. In summary, the silence of STAT3 suppressed metastasis and progression of CCA cells by regulating miR200c through the c-Myb mediated MEK/ERK pathway, suggesting STAT3 is the effective target for CCA arising from CC.
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