Abstract
The epithelial-mesenchymal transition (EMT) is the key process that drives tumor metastasis. Accumulating evidence suggests that the deregulation of some microRNAs (miRNAs), is implicated in this process. Here, we highlight the function and molecular mechanism of miR-630 and its potential clinical application in hepatocellular carcinoma (HCC). First, we identified the clinical relevance of miR-630 expression in a screen of 97 HCC patient tissues. Patients with low miR-630 expression had higher recurrence rates and shorter overall survival than those with high miR-630 expression. Functional studies demonstrated the overexpression of miR-630 in HCC cells attenuated the EMT phenotype in vitro. Conversely, inhibition of miR-630 promoted EMT in HCC cells. Mechanistically, our data revealed that miR-630 suppressed EMT by targeting Slug. Knockdown of Slug expression reversed miR-630 inhibitor-mediated EMT progression. Furthermore, we found that the TGF-β-Erk/SP1 and JNK/c-Jun signaling pathways repressed miR-630 transcription through occupying transcription factor binding sites. Ectopic expression of miR-630 restored the TGF-β-activated EMT process. Taken together, these findings demonstrate, in HCC cells, miR-630 exerts its tumor-suppressor functions through the TGF-β-miR-630-Slug axis and provides a potential prognostic predictor for HCC patients.
Highlights
Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide [1, 2]
Decreased miR-630 expression levels correlate with poor hepatocellular carcinoma (HCC) prognosis, suggesting that inhibition of miR-630 expression may contribute to the progression of HCC
In this study of HCC tissues, we found that miR630 expression was inversely correlated with metastasis, Edmondson-Steiner tumor grade, TNM stage and Barcelona-Clinic Liver Cancer www.impactjournals.com/oncotarget (BCLC) stage
Summary
Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide [1, 2]. Accumulating evidence has shown that miRNA dysfunction plays an important role in many diseases, including hepatic carcinogenesis. They function as oncogenes and contribute to proliferation and metastasis in HCC [6,7,8]. MiR-630 has been reported to exert pleiotropic functions and affect proliferation, metastasis, and apoptosis, thereby acting as either an oncogene or a tumor suppressor in different cellular contexts. Through targeting the oncogenes LMO3, metadherin, CDC7 www.impactjournals.com/oncotarget kinase, and IGF-1R, miR-630 has been demonstrated to be a tumor suppressor gene that represses cancer cell proliferation and metastasis or induces apoptosis and death in lung, breast, and pancreatic cancers [9,10,11,12,13]. We investigated the biological functions and the underlying molecular mechanisms of miR-630 in human HCC
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
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.
