The functional significance of miR-1 and miR-133a in renal cell carcinoma

被引：118

作者：

Kawakami, Kazumori ^{[1
]}

Enokida, Hideki ^{[1
]}

Chiyomaru, Takeshi ^{[1
]}

Tatarano, Shuichi ^{[1
]}

Yoshino, Hirofumi ^{[1
]}

Kagara, Ichiro ^{[1
]}

Gotanda, Takenari ^{[1
]}

Tachiwada, Tokushi ^{[1
]}

Nishiyama, Kenryu ^{[1
]}

Nohata, Nijiro ^{[2
]}

Seki, Naohiko ^{[2
]}

Nakagawa, Masayuki ^{[1
]}

机构：

[1] Kagoshima Univ, Dept Urol, Grad Sch Med & Dent Sci, Kagoshima 8908520, Japan

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

来源：

EUROPEAN JOURNAL OF CANCER | 2012年 / 48卷 / 06期

关键词：

TAGLN2; MicroRNA; MiR-1; MiR-133a; Renal cell cancer; MICRORNA EXPRESSION; BLADDER-CANCER; DOWN-REGULATION; IDENTIFICATION; SIGNATURES; PROFILES; FSCN1;

D O I：

10.1016/j.ejca.2011.06.030

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Purpose: The aim of this study was to find a novel molecular network involved in renal cell carcinoma (RCC) development through investigating the functions of miR-1 and miR-133a and their target genes. Methods: We checked the expression levels of miR-1 and miR-133a in RCC cell lines and specimens (N = 40) using real time RT-PCR. MiR-1 and miR-133a transfectants were subjected to a gain-of-function study to identify the functions of the miRNAs. To find the target genes of the miRNAs, we analysed the gene expression profile of their transfectants and performed a luciferase reporter assay. mRNA expression levels of the candidate target gene in the clinical specimens were examined, and loss-of-function studies were performed. Results: The expression levels of miR-1 and miR-133a were significantly suppressed in RCC cell lines and specimens. Ectopic restoration of miR-1 and miR-133a showed significant inhibition of cell proliferation and invasion, and moreover, revealed induction of apoptosis and cell cycle arrest. The luciferase assay revealed transgelin-2 (TAGLN2), selected as a target gene for miR-1 and miR-133a on the basis of the gene expression profile, to be directly regulated by both miR-1 and miR-133a. The loss-of-function studies showed significant inhibitions of cell proliferation and invasion in the si-TAGLN2 transfectant. The expression level of TAGLN2 mRNA was significantly up-regulated in the RCC specimens; in addition, there was a statistically significant inverse correlation between TAGLN2 and miR-1 and miR-133a expression. Conclusions: Our data indicate that up-regulation of the oncogenic TAGLN2 was due to down-regulation of tumour-suppressive miR-1 and miR-133a in human RCC. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：827 / 836

页数：10