The tumor-suppressive microRNA-143/145 cluster inhibits cell migration and invasion by targeting GOLM1 in prostate cancer

被引：105

作者：

Kojima, Satoko ^{[1
]}

Enokida, Hideki ^{[2
]}

Yoshino, Hirofumi ^{[2
]}

Itesako, Toshihiko ^{[2
]}

Chiyomaru, Takeshi ^{[2
]}

Kinoshita, Takashi ^{[3
]}

Fuse, Miki ^{[3
]}

Nishikawa, Rika ^{[3
]}

Goto, Yusuke ^{[3
]}

Naya, Yukio ^{[1
]}

Nakagawa, Masayuki ^{[2
]}

Seki, Naohiko ^{[3
]}

机构：

[1] Teikyo Univ Chiba Med Ctr, Dept Urol, Chiba, Japan

[2] Kagoshima Univ, Grad Sch Med & Dent Sci, Dept Urol, Kagoshima 890, Japan

[3] Chiba Univ, Grad Sch Med, Dept Funct Genom, Chiba 2608670, Japan

来源：

JOURNAL OF HUMAN GENETICS | 2014年 / 59卷 / 02期

关键词：

GOLM1; microRNA; miR-143; miR-145; prostate cancer; tumor suppressor; GOLGI PHOSPHOPROTEIN 2; EXPRESSION; MICRORNAS; MIR-133A; MECHANISMS; BIOMARKER; MIRNAS; TISSUE; GP73;

D O I：

10.1038/jhg.2013.121

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Our recent study of microRNA (miRNA) expression signature of prostate cancer (PCa) has revealed that the microRNA-143/145 (miR-143/145) cluster is significantly downregulated in cancer tissues, suggesting that these cluster miRNAs are candidate tumor suppressors. The aim of this study was to investigate the functional significance of the miR-143/145 cluster in PCa cells and to identify novel targets regulated by these cluster miRNAs in PCa. Restoration of miR-143 or miR-145 in PCa cell lines (PC3 and DU145) revealed that these miRNAs significantly inhibited cancer cell migration and invasion. Gene expression data and in silico analysis demonstrated that Golgi membrane protein 1 (GOLM1) resembling a type II golgi transmembrane protein was a potential target of miR-143/145 cluster target gene. Gene expression studies and luciferase reporter assays showed that GOLM1 was directly regulated by the miR-143/145 cluster. Silencing of GOLM1 resulted in significant inhibition of cell migration and invasion in PCa cells. Furthermore, the expression of GOLM1 was upregulated in cancer tissues by immunohistochemistry. Loss of the tumor-suppressive miR-143/145 cluster enhanced cancer cell migration and invasion in PCa through directly regulating GOLM1. Our data on target genes regulated by the tumor-suppressive miR-143/145 cluster provide new insights into the potential mechanisms of PCa oncogenesis and metastasis.

引用

页码：78 / 87

页数：10

共 32 条

[1] Endosomal trafficking and proprotein convertase cleavage of cis Golgi protein GP73 produces marker for hepatocellular carcinoma [J].