| First Author | Hu J | Year | 2017 |
| Journal | J Cell Sci | Volume | 130 |
| Issue | 19 | Pages | 3399-3413 |
| PubMed ID | 28818997 | Mgi Jnum | J:245480 |
| Mgi Id | MGI:5915660 | Doi | 10.1242/jcs.202127 |
| Citation | Hu J, et al. (2017) The CCR2 3'UTR functions as a competing endogenous RNA to inhibit breast cancer metastasis. J Cell Sci 130(19):3399-3413 |
| abstractText | Diverse RNA transcripts acting as competing endogenous RNAs (ceRNAs) can co-regulate each other's expression by competing for shared microRNAs. CCR2 protein, the receptor for CCL2, is implicated in cancer progression. However, we found that a higher CCR2 mRNA level is remarkably associated with prolonged survival of breast cancer patients. These conflicting results prompted us to study the non-coding function of CCR2 mRNA. We found that the CCR2 3' untranslated region (UTR) inhibited MDA-MB-231 and MCF-7 cell metastasis by repressing epithelial-mesenchymal transition (EMT) in vitro, and suppressed breast cancer metastasis in vivo Mechanistically, the CCR2 3'UTR modulated the expression of the RhoGAP protein STARD13 via acting as a STARD13 ceRNA in a microRNA-dependent and protein coding-independent manner. The CCR2 3'UTR blocked the activation of RhoA-ROCK1 pathway, which is the downstream effector of STARD13, and thus decreased the phosphorylation level of myosin light chain 2 (MLC2) and formation of F-actin. Additionally, the function of the CCR2 3'UTR was dependent on STARD13 expression. In conclusion, our results confirmed that the CCR2 3'UTR acts as a metastasis suppressor by acting as a ceRNA for STARD13 and thus inhibiting RhoA-ROCK1-MLC-F-actin pathway in breast cancer cells.This article has an associated First Person interview with the first author of the paper. |
