MicroRNA-409 suppresses tumour cell invasion and metastasis by directly targeting radixin in gastric cancers

B. Zheng, L. Liang, S. Huang, R. Zha, L. Liu, D. Jia, Q. Tian, Q. Wang, C. Wang, Z. Long, Y. Zhou, X. Cao, C. Du, Y. Shi, X. He

Research output: Contribution to journalArticle

91 Citations (Scopus)

Abstract

Emerging evidence has shown that aberrantly expressed microRNAs (miRNAs) are highly associated with tumour development and progression. However, little is known about the potential role of miRNAs in gastric cancer (GC) metastasis. In this study, miR-409-3p was found to be downregulated frequently in human GCs, and its expression was significantly associated with tumor-node-metastasis (TNM) stage and lymph node metastasis. Enforced expression of miR-409 in GC cells significantly reduced their migration and invasion in vitro and their capacity to develop distal pulmonary metastases and peritoneal dissemination in vivo. Moreover, we found that miR-409 exerted its function predominantly through the mature miR-409-3p, but not miR-409-5p. Microarray and bioinformatics analysis identified the pro-metastatic gene radixin (RDX) as a potential miR-409-3p target. Further studies confirmed that miR-409-3p suppressed the expression of RDX by directly binding to its 3′-untranslated region. Silencing of RDX by small interfering RNAs phenocopied the effects of miR-409 overexpression, whereas restoration of RDX in miR-409-overexpressed GC cells reversed the suppressive effects of miR-409. Taken together, these results demonstrate that miR-409 suppresses GC cell invasion and metastasis by directly targeting RDX and that patients with downregulated miR-409-3p are prone to lymph node metastasis.

Original languageEnglish (US)
Pages (from-to)4509-4516
Number of pages8
JournalOncogene
Volume31
Issue number42
DOIs
StatePublished - Oct 18 2012

Fingerprint

MicroRNAs
Stomach Neoplasms
Neoplasm Metastasis
Neoplasms
Down-Regulation
Lymph Nodes
3' Untranslated Regions
Microarray Analysis
Computational Biology
Small Interfering RNA
radixin
Lung
Genes

Keywords

  • gastric cancer
  • metastasis
  • microRNA-409
  • radixin

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

MicroRNA-409 suppresses tumour cell invasion and metastasis by directly targeting radixin in gastric cancers. / Zheng, B.; Liang, L.; Huang, S.; Zha, R.; Liu, L.; Jia, D.; Tian, Q.; Wang, Q.; Wang, C.; Long, Z.; Zhou, Y.; Cao, X.; Du, C.; Shi, Y.; He, X.

In: Oncogene, Vol. 31, No. 42, 18.10.2012, p. 4509-4516.

Research output: Contribution to journalArticle

Zheng, B, Liang, L, Huang, S, Zha, R, Liu, L, Jia, D, Tian, Q, Wang, Q, Wang, C, Long, Z, Zhou, Y, Cao, X, Du, C, Shi, Y & He, X 2012, 'MicroRNA-409 suppresses tumour cell invasion and metastasis by directly targeting radixin in gastric cancers', Oncogene, vol. 31, no. 42, pp. 4509-4516. https://doi.org/10.1038/onc.2011.581
Zheng, B. ; Liang, L. ; Huang, S. ; Zha, R. ; Liu, L. ; Jia, D. ; Tian, Q. ; Wang, Q. ; Wang, C. ; Long, Z. ; Zhou, Y. ; Cao, X. ; Du, C. ; Shi, Y. ; He, X. / MicroRNA-409 suppresses tumour cell invasion and metastasis by directly targeting radixin in gastric cancers. In: Oncogene. 2012 ; Vol. 31, No. 42. pp. 4509-4516.
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AB - Emerging evidence has shown that aberrantly expressed microRNAs (miRNAs) are highly associated with tumour development and progression. However, little is known about the potential role of miRNAs in gastric cancer (GC) metastasis. In this study, miR-409-3p was found to be downregulated frequently in human GCs, and its expression was significantly associated with tumor-node-metastasis (TNM) stage and lymph node metastasis. Enforced expression of miR-409 in GC cells significantly reduced their migration and invasion in vitro and their capacity to develop distal pulmonary metastases and peritoneal dissemination in vivo. Moreover, we found that miR-409 exerted its function predominantly through the mature miR-409-3p, but not miR-409-5p. Microarray and bioinformatics analysis identified the pro-metastatic gene radixin (RDX) as a potential miR-409-3p target. Further studies confirmed that miR-409-3p suppressed the expression of RDX by directly binding to its 3′-untranslated region. Silencing of RDX by small interfering RNAs phenocopied the effects of miR-409 overexpression, whereas restoration of RDX in miR-409-overexpressed GC cells reversed the suppressive effects of miR-409. Taken together, these results demonstrate that miR-409 suppresses GC cell invasion and metastasis by directly targeting RDX and that patients with downregulated miR-409-3p are prone to lymph node metastasis.

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