Page 222 - ebook

[B. Cell Biology/Stem Cell] B-46

Wnt signaling up-regulates microRNA-135b to promote

intestinal tumorigenesis

Tae-Su Han¹*

¹Biotherapeutics Translational Research Center, Korea Research Institute of Bioscience & Biotechnology, Daejeon

34141, Korea

Colorectal cancer (CRC) is one of the leading causes of cancer-related death, but little is known about changes in

microRNA expression patterns during CRC development. In this study, we examined the role of miR-135b in intestinal
tumorigenesis. Firstly, we found that the miR-135b was up-regulated in intestinal crypt cells compared with villus,

and Wnt3a treatment induced miR-135b in immortalized cells, suggesting that miR-135b can be regulated by Wnt
signaling. To examine the role of miR-135b in Wnt-driven intestinal tumorigenesis, the miR-135b expression level

was analyzed in adenomatous polyposis coli (Apcdelta716) mice, resulting in overexpression of miR-135b was
detected in intestinal tumor tissues compared with normal tissues. In addition, we also found that the miR-135b

was up-regulated in colitis-associated cancer (AOM/DSS mice). Notably, disruption of miR-135b in Apcdelta716 and
AOM/DSS mice significantly reduced the intestinal tumors. Ectopic expression of miR-135b in CRC cell lines

promoted cell migration and in vivo tumorigenesis. Mechanistically, FOXN3 and RECK as targets of miR-135b were
down-regulated and levels of these genes correlated inversely with levels of miR-135b in human CRC tumors. These

novel results suggest that miR-135b is a key regulator of CRC development via targeting tumor suppressor genes.