Year-end Sale % OFF 
Abstract
The activation of CXCL12/CXCR4 axis is associated with potential progression of cancer, such as invasion, metastasis and chemoresistance. However, the underlying mechanisms of CXCL12/CXCR4 axis and cancer progression have been poorly explored. We hypothesized that miRNAs might be critical downstream mediators of CXCL12/CXCR4 axis involved in cancer invasion and chemoresistance in CRC. In human CRC cells, we found that the activation of CXCL12/CXCR4 axis promoted epithelial-mesenchymal transition (EMT) and concurrent upregulation of miR-125b. Overexpression of miR-125b robustly triggered EMT and cancer invasion, which in turn enhanced the expression of CXCR4. Importantly, the reciprocal positive feedback loop between CXCR4 and miR-125b further activated the Wnt/β-catenin signaling by targeting Adenomatous polyposis coli (APC) gene. There was a negative correlation of the expression of miR-125b with APC mRNA in paired human colorectal tissue specimens. Further experiments indicated a role of miR-125b in conferring 5-fluorouracil (5-FU) resistance in CRC probably through increasing autophagy both in vitro and in vivo. MiR-125b functions as an important downstream mediator upon the activation of CXCL12/CXCR4 axis that involved in EMT, invasion and 5-FU resistance of CRC. These findings shed a new insight into the role of miR-125b and provide a potential therapeutic target in CRC.
Highlights
Colorectal cancer (CRC) is among three leading causes of cancer-related death worldwide
To explore the roles of miRNAs induced by the activation of CXCL12/CXCR4 axis in CRC, we firstly examined a variety of miRNAs upregulated or downregulated in HCT116 cells overexpressing CXCR4 by sequencing (Supplementary Table 1)
To investigate whether activation of CXCL12/CXCR4 axis promotes epithelial-mesenchymal transition (EMT), we performed the assays of RT-PCR and Western blot to determine the expressions of E-cadherin and vimentin in cancer cells
Summary
Colorectal cancer (CRC) is among three leading causes of cancer-related death worldwide. It has been proposed that activation of oncogenic Wnt/β-catenin and PI3K-Akt signaling, an epithelial-mesenchymal transition (EMT) and regulating cancer stem cells (CSCs) contributed to the initiation, progression and chemoresistance of CRC5. MicroRNAs (miRNAs) have been considered to play important roles in cancer progression by regulating target gene expression at the post-transcriptional level[9] They emerge as either tumor suppressors or oncomiRs broadly implicated in tumor proliferation, invasion and resistance to therapy[10]. The upregulation of miR-125b further activated the Wnt/β-catenin signaling by targeting APC gene and contributed to 5-FU resistance through enhancing cell autophagy. These results shed insights into the role of miR-125b upon activation of CXCL12/CXCR4 axis and provide potential therapeutic targets in CRC
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
