| First Author | Yu X | Year | 2019 |
| Journal | J Exp Clin Cancer Res | Volume | 38 |
| Issue | 1 | Pages | 32 |
| PubMed ID | 30678736 | Mgi Jnum | J:279148 |
| Mgi Id | MGI:6359337 | Doi | 10.1186/s13046-018-1014-x |
| Citation | Yu X, et al. (2019) CXCL12/CXCR4 promotes inflammation-driven colorectal cancer progression through activation of RhoA signaling by sponging miR-133a-3p. J Exp Clin Cancer Res 38(1):32 |
| abstractText | BACKGROUND: Activation of CXCL12/CXCR4 axis has been found to be associated with invasion and metastasis in many cancers. However, the underlying mechanism remains elusive. Increasing data highlight that non-coding RNAs are linked to CRC progression. METHODS: The effects of CXCR4 were investigated using villin-CXCR4 transgenic mice model by flow cytometry assay, immunohistochemistry, and Western blot. The mechanism was explored through bioinformatics, luciferase reporter assay and RNA immunoprecipitation assay. RESULTS: We found that high CXCR4 expression exacerbated colitis-associated cancer in villin-CXCR4 transgenic mice. CXCR4(+/-)Apc(min/+) compound mutant mice demonstrated higher colorectal tumorigenesis than Apc(min/+) mice. Furthermore, overexpression of CXCR4 was found to promote the epithelial-mesenchymal transition (EMT) and infiltration of myeloid-derived suppressor cells (MDSCs) and macrophages in colonic tissue, accelerating colitis-associated and Apc mutation-driven colorectal tumorigenesis and progression. Notably, miR-133a-3p was found to be significantly decreased in HCT116 cells overexpressing CXCR4 by miRNA sequencing. miR-133a-3p was proved to target RhoA, which is involved in cytoskeletal reorganization that drive cell motility. Importantly, CXCL12/CXCR4-induced upregulation of lncRNA XIST functioned as a ceRNA to sponge miR-133a-3p, thereby liberating the repression of RhoA by miR-133a-3p. The negative correlation of miR-133a-3p with RhoA was also confirmed in human CRC tissues and CXCR4(+/-) mice. CONCLUSIONS: Our findings revealed the critical role of CXCR4 in promoting progression of inflammatory colorectal cancer through recruiting immunocytes and enhancing cytoskeletal remodeling by lncRNA XIST/ miR-133a-3p/ RhoA signaling. These results provide novel potential therapeutic targets for hindering CXCL12/CXCR4-induced CRC progression. |
