MicroRNA-101 (miR-101) is rapidly earning a place in the “Who’s Who” of tumor suppressor genes. In November, we told you how The Little RNA that Could wallops prostate cancer by repressing the histone methyltransferase EZH2. Now researchers at the University of Southern California have shown that miR-101 plays a similar role in the suppression of bladder cancer.
miRNA profiling of bladder transitional cell carcinoma (TCC) samples revealed downregulation of miR-101. When the investigators restored miR-101 expression in TCC cells, tumor cell proliferation and colony formation were inhibited. An miRNA target prediction algorithm identified EZH2 as a potential target of miR-101. As the catalytic subunit of the Polycomb Repressive Complex 2, EZH2 silences target genes by trimethylating histone 3 lysine 27 (H3K27me3). EZH2 is overexpressed in several types of cancer, including TCC.
The investigators showed that miR-101 represses EZH2 and H3K27me3 by binding to the histone methyltransferase’s 3’UTR. Because miR-101 was shown to be downregulated in lung cancer, breast cancer, colorectal cancer, and now bladder cancer, the miRNA could be part of a solid tumor signature. See for yourself at Cancer Research, March 2009.