title: Effect of miR-122 and its target gene cationic amino acid transporter 1 on colorectal liver metastasis.
abstract: Control of liver metastasis is an important issue in the treatment of colorectal cancer (CRC). MicroRNAs have been shown to be involved in the development of many cancers, but little is known about their role in the process of colorectal liver metastasis. We compared miRNA expression between primary colorectal tumors and liver metastasis to identify those involved in the process of metastasis. Cancer cells were isolated from formalin-fixed paraffin-embedded primary CRC samples and their corresponding metastatic liver tumors in six patients using laser capture microdissection, and miRNA expression was analyzed using TaqMan miRNA arrays. The most abundant miRNA in liver metastasis compared with primary tumors was miR-122. Immunohistochemical analysis revealed that the expression levels of cationic amino acid transporter 1 (CAT1), a negative target gene of miR-122, were lower in liver metastases than primary tumors (P < 0.001). Expression levels of CAT1 in 132 primary tumors were negatively correlated with the existence of synchronous liver metastasis (P = 0.0333) and tumor stage (P < 0.0001). In an analysis of 121 colon cancer patients without synchronous liver metastasis, patients with CAT1-low colon cancer had significantly shorter liver metastasis-free survival (P = 0.0258) but not overall survival or disease-free survival. Overexpression of miR-122 and concomitant suppression of CAT1 in the primary tumor appears to play important roles in the development of colorectal liver metastasis. Expression of CAT1 in the primary CRC has the potential to be a novel biomarker to predict the risk of postoperative liver metastasis of CRC patients.
authors: Second Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors: Ichirota
authors: I
authors: Iino
authors: Hirotoshi
authors: H
authors: Kikuchi
authors: Shinichiro
authors: S
authors: Miyazaki
authors: Yoshihiro
authors: Y
authors: Hiramatsu
authors: Manabu
authors: M
authors: Ohta
authors: Kinji
authors: K
authors: Kamiya
authors: Yukiko
authors: Y
authors: Kusama
authors: Satoshi
authors: S
authors: Baba
authors: Mitsutoshi
authors: M
authors: Setou
authors: Hiroyuki
authors: H
authors: Konno
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015220:Calcium Channels / Q000235:genetics* / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000556:secondary*; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D050916:TRPV Cation Channels / Q000235:genetics* / Q000378:metabolism
chemical_list: D015220:Calcium Channels; C531907:MIRN122 microRNA, human; D035683:MicroRNAs; D050916:TRPV Cation Channels; C422827:TRPV6 protein, human
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