Abstract
MicroRNAs are well suited to regulate tumor metastasis because of their capacity to coordinately repress numerous target genes, thereby potentially enabling their intervention at multiple steps of the invasion-metastasis cascade. We identify a microRNA exemplifying these attributes, miR-31, whose expression correlates inversely with metastasis in human breast cancer patients. Overexpression of miR-31 in otherwise-aggressive breast tumor cells suppresses metastasis. We deploy a stable microRNA sponge strategy to inhibit miR-31 in vivo; this allows otherwise-nonaggressive breast cancer cells to metastasize. These phenotypes do not involve confounding influences on primary tumor development and are specifically attributable to miR-31-mediated inhibition of several steps of metastasis, including local invasion, extravasation or initial survival at a distant site, and metastatic colonization. Such pleiotropy is achieved via coordinate repression of a cohort of metastasis-promoting genes, including RhoA. Indeed, RhoA re-expression partially reverses miR-31-imposed metastasis suppression. These findings indicate that miR-31 uses multiple mechanisms to oppose metastasis.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1032-1046 |
| Number of pages | 15 |
| Journal | Cell |
| Volume | 137 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 12 2009 |
| Externally published | Yes |
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Keywords
- CELLBIO
- HUMDISEASE
- RNA
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
Cite this
A Pleiotropically Acting MicroRNA, miR-31, Inhibits Breast Cancer Metastasis. / Valastyan, Scott; Reinhardt, Ferenc; Benaich, Nathan; Calogrias, Diana; Szász, Attila M.; Wang, Zhigang C.; Brock, Jane E.; Richardson, Andrea; Weinberg, Robert A.
In: Cell, Vol. 137, No. 6, 12.06.2009, p. 1032-1046.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A Pleiotropically Acting MicroRNA, miR-31, Inhibits Breast Cancer Metastasis
AU - Valastyan, Scott
AU - Reinhardt, Ferenc
AU - Benaich, Nathan
AU - Calogrias, Diana
AU - Szász, Attila M.
AU - Wang, Zhigang C.
AU - Brock, Jane E.
AU - Richardson, Andrea
AU - Weinberg, Robert A.
PY - 2009/6/12
Y1 - 2009/6/12
N2 - MicroRNAs are well suited to regulate tumor metastasis because of their capacity to coordinately repress numerous target genes, thereby potentially enabling their intervention at multiple steps of the invasion-metastasis cascade. We identify a microRNA exemplifying these attributes, miR-31, whose expression correlates inversely with metastasis in human breast cancer patients. Overexpression of miR-31 in otherwise-aggressive breast tumor cells suppresses metastasis. We deploy a stable microRNA sponge strategy to inhibit miR-31 in vivo; this allows otherwise-nonaggressive breast cancer cells to metastasize. These phenotypes do not involve confounding influences on primary tumor development and are specifically attributable to miR-31-mediated inhibition of several steps of metastasis, including local invasion, extravasation or initial survival at a distant site, and metastatic colonization. Such pleiotropy is achieved via coordinate repression of a cohort of metastasis-promoting genes, including RhoA. Indeed, RhoA re-expression partially reverses miR-31-imposed metastasis suppression. These findings indicate that miR-31 uses multiple mechanisms to oppose metastasis.
AB - MicroRNAs are well suited to regulate tumor metastasis because of their capacity to coordinately repress numerous target genes, thereby potentially enabling their intervention at multiple steps of the invasion-metastasis cascade. We identify a microRNA exemplifying these attributes, miR-31, whose expression correlates inversely with metastasis in human breast cancer patients. Overexpression of miR-31 in otherwise-aggressive breast tumor cells suppresses metastasis. We deploy a stable microRNA sponge strategy to inhibit miR-31 in vivo; this allows otherwise-nonaggressive breast cancer cells to metastasize. These phenotypes do not involve confounding influences on primary tumor development and are specifically attributable to miR-31-mediated inhibition of several steps of metastasis, including local invasion, extravasation or initial survival at a distant site, and metastatic colonization. Such pleiotropy is achieved via coordinate repression of a cohort of metastasis-promoting genes, including RhoA. Indeed, RhoA re-expression partially reverses miR-31-imposed metastasis suppression. These findings indicate that miR-31 uses multiple mechanisms to oppose metastasis.
KW - CELLBIO
KW - HUMDISEASE
KW - RNA
UR - http://www.scopus.com/inward/record.url?scp=66449095667&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=66449095667&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2009.03.047
DO - 10.1016/j.cell.2009.03.047
M3 - Article
C2 - 19524507
AN - SCOPUS:66449095667
VL - 137
SP - 1032
EP - 1046
JO - Cell
JF - Cell
SN - 0092-8674
IS - 6
ER -