Ratio of miR-196s to HOXC8 messenger RNA correlates with breast cancer cell migration and metastasis

Yong Li, Maoxiang Zhang, Huijun Chen, Zheng Dong, Vadivel Ganapathy, Muthusamy Thangaraju, Shuang Huang

Research output: Contribution to journalArticle

114 Citations (Scopus)

Abstract

Expression profiling has identified metastasis-associated microRNAs (miRNA) but technical limitations hinder the discovery of metastasis-suppressing miRNAs. In this study, we sought metastasis-suppressing miRNAs by functional screening. Individual miRNAs were lentivirally introduced into metastatic MDA-MB-231 breast cancer cells and analyzed for effects on cell migration, a critical step in cancer metastasis. Among 486 miRNAs screened, 14 were identified that included all of the members of the miRNA-196 family (miR-196a1, miR-196a2, and miR-196b). Enforced expression of miR-196a1/2 or miR-196b abrogated in vitro invasion and in vivo spontaneous metastasis of breast cancer cells, indicating that members of the miR-196 family are potent metastasis suppressors. We found that miR-196 inhibited the expression of transcription factor HOXC8. Functional linkage was implied by small interfering RNA-mediated knockdown of HOXC8, which suppressed cell migration and metastasis, and by ectopic expression of HOXC8, which prevented the effects of miR-196 on cell migration and metastasis. Unlike other metastasis-associated miRNAs that have been described, the expressions of miR-196 were not correlated with breast cancer cell migration or the metastatic status of clinical breast tumor specimens. Instead, we detected an excellent correlation between the ratio of miR-196 to HOXC8 messages and the migratory behavior of breast cancer cell lines as well as the metastatic status of clinical samples. Our findings identify miRNA-196s as potent metastasis suppressors and reveal that the ratio of miR-196s to HOXC8 mRNA might be an indicator of the metastatic capability of breast tumors.

Original languageEnglish (US)
Pages (from-to)7894-7904
Number of pages11
JournalCancer Research
Volume70
Issue number20
DOIs
StatePublished - Oct 15 2010

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Cell Movement
MicroRNAs
Breast Neoplasms
Neoplasm Metastasis
Messenger RNA
Small Interfering RNA
Transcription Factors
Cell Line

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Ratio of miR-196s to HOXC8 messenger RNA correlates with breast cancer cell migration and metastasis. / Li, Yong; Zhang, Maoxiang; Chen, Huijun; Dong, Zheng; Ganapathy, Vadivel; Thangaraju, Muthusamy; Huang, Shuang.

In: Cancer Research, Vol. 70, No. 20, 15.10.2010, p. 7894-7904.

Research output: Contribution to journalArticle

Li, Yong ; Zhang, Maoxiang ; Chen, Huijun ; Dong, Zheng ; Ganapathy, Vadivel ; Thangaraju, Muthusamy ; Huang, Shuang. / Ratio of miR-196s to HOXC8 messenger RNA correlates with breast cancer cell migration and metastasis. In: Cancer Research. 2010 ; Vol. 70, No. 20. pp. 7894-7904.
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