Abstract
The Polycomb Repressive Complex 2 (PRC2) mediates epigenetic gene silencing by trimethylating histone H3 lysine 27 (H3K27me3) and is known to aberrantly silence tumor suppressor genes in cancer. EZH2, the catalytic subunit of PRC2, enhances tumorigenesis and is commonly overexpressed in several types of cancer. Our microRNA profiling of bladder transitional cell carcinoma (TCC) patient samples revealed that microRNA-101 (miR-101) is down-regulated in TCC, and we showed that miR-101 inhibits cell proliferation and colony formation in TCC cell lines. Furthermore, our results confirm that miR-101 directly represses EZH2 and stable EZH2 knockdowns in TCC cell lines create a similar growth suppressive phenotype. This suggests that abnormal down-regulation of miR-101 could lead to the overexpression of EZH2 frequently seen in cancer. We conclude that miR-101 may be a potent tumor suppressor by altering global chromatin structure through repression of EZH2.
Highlights
Polycomb group proteins are chromatin-modifying enzymes that are important in stem cell maintenance, X-inactivation, imprinting, and development, and many Polycomb group proteins are dysregulated in cancer [1]
The Polycomb group protein EZH2 is the catalytic subunit of the Polycomb Repressive Complex 2 (PRC2), which is a critical part of the cellular machinery involved in epigenetically regulating gene transcription [2]
The miRNA that was most down-regulated in transitional cell carcinoma (TCC), miR-1, and miR-29c were downregulated in hepatocellular carcinoma and lung cancer, respectively [20, 21]
Summary
Polycomb group proteins are chromatin-modifying enzymes that are important in stem cell maintenance, X-inactivation, imprinting, and development, and many Polycomb group proteins are dysregulated in cancer [1]. Restored expression of miRNAs in TCC cell lines reveals putative tumor suppressors. MiR-1, miR-101, miR-127, miR-143, and miR-145 were expressed at low levels in all cell lines (data not shown), indicating that these miRNAs are promising tumor suppressor candidates.
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.
