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Int J Mol Sci. 2017 Sep 13;18(9). pii: E1969. doi: 10.3390/ijms18091969.

Dual Strands of Pre-miR-149 Inhibit Cancer Cell Migration and Invasion through Targeting FOXM1 in Renal Cell Carcinoma.

Author information

1
Department of Functional Genomics, Chiba University Graduate School of Medicine, 2608670 Chiba, Japan. aexa5919@chiba-u.jp.
2
Department of Urology, Chiba University Graduate School of Medicine, 2608670 Chiba, Japan. aexa5919@chiba-u.jp.
3
Department of Functional Genomics, Chiba University Graduate School of Medicine, 2608670 Chiba, Japan. agda0043@chiba-u.jp.
4
Department of Urology, Chiba University Graduate School of Medicine, 2608670 Chiba, Japan. agda0043@chiba-u.jp.
5
Department of Functional Genomics, Chiba University Graduate School of Medicine, 2608670 Chiba, Japan. yasutaka1205@chiba-u.jp.
6
Department of Urology, Chiba University Graduate School of Medicine, 2608670 Chiba, Japan. yasutaka1205@chiba-u.jp.
7
Department of Functional Genomics, Chiba University Graduate School of Medicine, 2608670 Chiba, Japan. afha7393@chiba-u.jp.
8
Department of Urology, Chiba University Graduate School of Medicine, 2608670 Chiba, Japan. afha7393@chiba-u.jp.
9
Department of Functional Genomics, Chiba University Graduate School of Medicine, 2608670 Chiba, Japan. aeha4003@chiba-u.jp.
10
Department of Biomedical Science, Chiba University Graduate School of Medicine, 2608670 Chiba, Japan. lisaf1227@faculty.chiba-u.jp.
11
Department of Functional Genomics, Chiba University Graduate School of Medicine, 2608670 Chiba, Japan. adfa2718@chiba-u.jp.
12
Department of Functional Genomics, Chiba University Graduate School of Medicine, 2608670 Chiba, Japan. mayukokato@chiba-u.jp.
13
Department of Urology, Teikyo University Chiba Medical Center, 2990111 Ichihara, Japan. kojima-s@med.teikyo-u.ac.jp.
14
Department of Urology, Teikyo University Chiba Medical Center, 2990111 Ichihara, Japan. nayay@med.teikyo-u.ac.jp.
15
Department of Urology, Chiba University Graduate School of Medicine, 2608670 Chiba, Japan. tomohiko_ichikawa@faculty.chiba-u.jp.
16
Department of Functional Genomics, Chiba University Graduate School of Medicine, 2608670 Chiba, Japan. naoseki@faculty.chiba-u.jp.

Abstract

Our recent studies revealed that dual strands of certain pre-microRNAs, e.g., pre-miR-144, pre-miR-145, and pre-miR-150, act as antitumor microRNAs (miRNAs) in several cancers. The involvement of passenger strands of miRNAs in cancer pathogenesis is a novel concept in miRNA research. The analysis of a miRNA expression signature in clear cell renal cell carcinoma (ccRCC) has revealed that the guide strand of pre-miR-149 is significantly downregulated in cancer tissues. The aims of this study were to investigate the functional significance of miR-149's guide strand (miR-149-5p) and passenger strand (miR-149-3p), and to identify the oncogenic genes regulated by these miRNAs in ccRCC cells. The ectopic expression of these miRNAs significantly inhibited cancer cell migration and invasion in ccRCC cells. Forkhead box protein M1 (FOXM1) was directly regulated by miR-149-5p and miR-149-3p in ccRCC cells. Knockdown studies using si-FOXM1 showed that the expression of FOXM1 enhanced RCC cell aggressiveness. Interestingly, the analysis of a large number of patients in the The Cancer Genome Atlas (TCGA) database (n = 260) demonstrated that patients with high FOXM1 expression had significantly shorter survival than did those with low FOXM1 expression (p = 1.5 × 10⁻⁶). Taken together, dual strands of pre-miR-149 (miR-149-5p and miR-149-3p) acted as antitumor miRNAs through the targeting of FOXM1 in ccRCC cells.

KEYWORDS:

FOXM1; antitumor; clear cell renal cell carcinoma; miR-149-3p; miR-149-5p; microRNA

PMID:
28902136
PMCID:
PMC5618618
DOI:
10.3390/ijms18091969
[Indexed for MEDLINE]
Free PMC Article

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