A Pleiotropically Acting microRNA, miR-31, Inhibits Breast Cancer Metastasis
By Scott Valastyan, Ferenc Reinhardt, Nathan Benaich, Diana Calogrias, A. Szász, Z. Wang, J. Brock, A. Richardson, R. Weinberg. Cell, 2009
877 citations recorded by the source corpus.
SUMMARY MicroRNAs are well-suited to regulate tumor metastasis due to 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 stably inhibit miR-31 in vivo; this allows otherwise-non-aggressive 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.
Subfields: Cancer Research, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/d97fcec44f07e79d1d15e4d1e689b1a8a0a98d63
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Citations in the corpus
- Improved classification of breast cancer by analysis of genetic alterations and gene expression profiling (2011, positive): “For example, over-expression/ knockdown of several miRNAs, including miR-10b, miR-9, miR-31, miR-126 and miR-335, was shown to play a role in metastasis (15, 26, 27, 16).”
- MicroRNAs en route to the clinic: progress in validating and targeting microRNAs for cancer therapy (2011, positive): “miR-31 expression is decreased in metastatic human breast cancer samples and has been confirmed to have an important role in metastasi”
- MicroRNAs in development and disease. (2011, neutral): “While exhibiting 4-fold downregulation in nonmetastatic cancer cells relative to noncancerous cells, it is 100-fold reduced in metastatic cells (624).”
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- Targeting mitochondrial glutaminase activity inhibits oncogenic transformation (2010, neutral): “In particular, two members of the family, RhoA and RhoC, have been linked to the progression of malignancy, i.e., poorly differentiated pheno- types, local invasiveness, and metastasis (Kleer et al., 2002; Clark et al., 2000; Burbelo et al., 2004; Valastyan et al., 2009).”
- Most Random Gene Expression Signatures Are Significantly Associated with Breast Cancer Outcome (2011, neutral): “These include signatures of stem cells [13–15], aneuploidy [16], wound healing [17,18], hypoxia [19,20], stromal component [21], epithelialmesenchymal transition [22–24]; of mutations in TP53 [25], ALK5 [26]; of loss of PTEN [27]; of perturbations of E2F1 [28], bromodomain 4 [29], mir31 targets [30]”
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- miR-34 – a microRNA replacement therapy is headed to the clinic (2012, neutral): “…| Volume 3 | Article 120 | 1 “fgene-03-00120” — 2012/6/29 — 15:59 — page 2 — #2 tumor suppressive and oncogenic functions, or assume roles in diseases outside oncology which makes their practical application as cancer therapeutics difficult to predict (Valastyan et al., 2009; Liu et al., 2010).”