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MicroRNA-372 Is Associated with Poor Prognosis in Colorectal Cancer

2012; Karger Publishers; Volume: 82; Issue: 4 Linguagem: Inglês

10.1159/000336809

1423-0232

Shinya Yamashita, Hirofumi Yamamoto, Koshi Mimori, Naohiro Nishida, Hidekazu Takahashi, Naotsugu Haraguchi, Fumiaki Tanaka, Kohei Shibata, Mitsugu Sekimoto, Hideshi Ishii, Yuichiro� Doki, Masaki Mori,

Cancer-related molecular mechanisms research

<i>Objective:</i> MicroRNA-372 <i>(miR-372)</i> is reportedly shown to be an oncogene in human testicular germ cell tumors and gastric cancers, but its expression in colorectal cancer (CRC) is not yet determined. This study investigated the clinical significance of <i>miR-372</i> expression in CRC. <i>Methods: </i>qRT-PCR was used to evaluate <i>miR-372</i> in 144 CRC patients, and large tumor suppressor 2 <i>(LATS2)</i> expression was also examined as the likely target gene of <i>miR-372</i>. In vitroassays were performed to evaluate the biological function of<i> miR-372. </i><i>Results: </i>Multivariate analysis indicated that high<i> miR-372</i> expression was an independent prognostic factor (p = 0.006). High <i>miR-372</i> expression was associated with synchronous liver metastasis (p = 0.035). We found an inverse relationship between<i> miR-372 </i>and <i>LATS2 by</i> qRT-PCR (p = 0.007) and immunohistochemistry (p = 0.042) using CRC tissue samples. Furthermore, pre-miR-372 led to a decrease in the LATS2 protein and an increase in proliferative activity of LoVo cells. We also found a significant association between low <i>LATS2</i> expression and liver metastasis (p = 0.042). <i>Conclusions:</i> This study suggested that <i>miR-372</i> was a novel independent prognostic factor in CRC. Our data suggest that <i>LATS2 </i>may serve as one of the target genes of <i>miR-372 </i>in clinical CRC tissues.