MicroRNA-301 Mediates Proliferation and Invasion in Human Breast Cancer

Department of Medical Biophysics, Ontario Cancer Institute, University Health Network, University of Toronto, Toronto, Canada.
Cancer Research (Impact Factor: 9.33). 03/2011; 71(8):2926-37. DOI: 10.1158/0008-5472.CAN-10-3369
Source: PubMed


Several microRNAs have been implicated in human breast cancer but none to date have been validated or utilized consistently in clinical management. MicroRNA-301 (miR-301) overexpression has been implicated as a negative prognostic indicator in lymph node negative (LNN) invasive ductal breast cancer, but its potential functional impact has not been determined. Here we report that in breast cancer cells, miR-301 attenuation decreased cell proliferation, clonogenicity, migration, invasion, tamoxifen resistance, tumor growth, and microvessel density, establishing an important oncogenic role for this gene. Algorithm-based and experimental strategies identified FOXF2, BBC3, PTEN, and COL2A1 as candidate miR-301 targets, all of which were verified as direct targets through luciferase reporter assays. We noted that miR-301 is located in an intron of the SKA2 gene which is responsible for kinetochore assembly, and both genes were found to be coexpressed in primary breast cancer samples. In summary, our findings define miR-301 as a crucial oncogene in human breast cancer that acts through multiple pathways and mechanisms to promote nodal or distant relapses.

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Available from: Nehad M Alajez
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    • "In concordance with our results in GIST, miR-301a-3p overexpression was found in metastatic breast cancer (Shi et al, 2011). Functionally, miR-301a-3p has been demonstrated to promote cell growth, migration and invasion in breast cancer cells (Shi et al, 2011) and hepatocellular carcinoma cells (Zhou et al, 2012). These findings support the role of miR-301a-3p as an oncogene in progression and development of metastasis in various cancer types. "
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    • "In contrast, MCF-Exo contains higher amounts of mir-301a. The mir-301a over expression has been implicated as a negative prognostic indicator in lymph node negative (LNN) invasive ductal breast cancer [35]. MCF-Exo also contains mir-34a, which regulates several genes including p53 [36]. "
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    • "Aberrant expression of miRNAs has frequently been reported in cancer [4-7] and miRNAs are thus suggested to play potential oncogenic or tumor-suppressive roles. In breast cancer, altered miRNA expression has been associated with, for example, estrogen receptor (ER) signaling [8-10], proliferation [4,11,12] and metastasis [13-16]. The underlying mechanisms of aberrant miRNA expression are poorly understood, but likely causes include DNA copy number aberrations, mutations, epigenetic aberrations, dysregulation of transcription factors targeting miRNAs and alterations in the miRNA biogenesis pathway [17]. "
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