MicroRNAs at the human 14q32 locus have prognostic significance in osteosarcoma. Orphanet J Rare Dis 8:7

Orphanet Journal of Rare Diseases (Impact Factor: 3.36). 01/2013; 8(1):7. DOI: 10.1186/1750-1172-8-7
Source: PubMed

ABSTRACT Background
Deregulation of microRNA (miRNA) transcript levels has been observed in many types of tumors including osteosarcoma. Molecular pathways regulated by differentially expressed miRNAs may contribute to the heterogeneous tumor behaviors observed in naturally occurring cancers. Thus, tumor-associated miRNA expression may provide informative biomarkers for disease outcome and metastatic potential in osteosarcoma patients. We showed previously that clusters of miRNAs at the 14q32 locus are downregulated in human osteosarcoma.

Human and canine osteosarcoma patient’s samples with clinical follow-up data were used in this study. We used bioinformatics and comparative genomics approaches to identify miRNA based prognostic biomarkers in osteosarcoma. Kaplan-Meier survival curves and Whitney Mann U tests were conducted for validating the statistical significance.

Here we show that an inverse correlation exists between aggressive tumor behavior (increased metastatic potential and accelerated time to death) and the residual expression of 14q32 miRNAs (using miR-382 as a representative of 14q32 miRNAs) in a series of clinically annotated samples from human osteosarcoma patients. We also show a comparable decrease in expression of orthologous 14q32 miRNAs in canine osteosarcoma samples, with conservation of the inverse correlation between aggressive behavior and expression of orthologous miRNA miR-134 and miR-544.

We conclude that downregulation of 14q32 miRNA expression is an evolutionarily conserved mechanism that contributes to the biological behavior of osteosarcoma, and that quantification of representative transcripts from this family, such as miR-382, miR-134, and miR-544, provide prognostic and predictive markers that can assist in the management of patients with this disease.

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Available from: Pancras C W Hogendoorn, Sep 28, 2015
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    • "Loss of epithelial characteristics is also induced by miR-382 in renal interstitial fibrosis (43). MicroRNAs in chromosome 14q32 locus are downregulated in osteosarcomas, suggesting that these 14q32 microRNAs, including miR-382, potentially target the cMyc transcript and that the microRNAs-cMyc gene network is deregulated during the pathogenesis of osteosarcoma (44,45). The involvement of miR-382 has also been reported during leukemogenesis (46). "
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    • "To date, miR144 has no documented role in OvCa tumors, but low miR144 levels are independently prognostic of poor outcome in primary colorectal cancers [50]. Decrease in miR382 expression has been correlated with poor outcomes in osteosarcomas [51]. miR382 is located at the 14q32 locus, which has been shown to be lost in primary OvCa tumors [52]; our results are the first evidence confirming miR382 as a novel oncogenic regulator within that region. "
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    PLoS ONE 03/2014; 9(3):e91540. DOI:10.1371/journal.pone.0091540 · 3.23 Impact Factor
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    • "miR-134 is located on chromosome 14q32.31, which is frequently lost in gastrointestinal stromal tumors (GISTs) [24], and its expression is often decreased in GIST, osteosarcoma, glioma and HCC [17], [24], [25], [26]. Boominathan reported that TA-p73 may regulate the post-transcriptional processing of miR-134 by increasing Ago1/2 activity, thereby repressing cancer stem cell proliferation [27]. "
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