Modulation of the Osteosarcoma Expression Phenotype by MicroRNAs

Abstract

BackgroundOsteosarcomas are the most common primary malignant tumors of bone and show multiple and complex genomic aberrations. miRNAs are non-coding RNAs capable of regulating gene expression at the post transcriptional level, and miRNAs and their target genes may represent novel therapeutic targets or biomarkers for osteosarcoma. In order to investigate the involvement of miRNAs in osteosarcoma development, global microarray analyses of a panel of 19 human osteosarcoma cell lines was performed.Principal findingsWe identified 177 miRNAs that were differentially expressed in osteosarcoma cell lines relative to normal bone. Among these, miR-126/miR-126*, miR-142-3p, miR-150, miR-223, miR-486-5p and members of the miR-1/miR-133a, miR-144/miR-451, miR-195/miR-497 and miR-206/miR-133b clusters were found to be downregulated in osteosarcoma cell lines. All miRNAs in the paralogous clusters miR-17-92, miR-106b-25 and miR-106a-92 were overexpressed. Furthermore, the upregulated miRNAs included miR-9/miR-9*, miR-21*, miR-31/miR-31*, miR-196a/miR-196b, miR-374a and members of the miR-29 and miR-130/301 families. The most interesting inversely correlated miRNA/mRNA pairs in osteosarcoma cell lines included miR-9/TGFBR2 and miR-29/p85α regulatory subunit of PI3K. PTEN mRNA correlated inversely with miR-92a and members of the miR-17 and miR-130/301 families. Expression profiles of selected miRNAs were confirmed in clinical samples. A set of miRNAs, miR-1, miR-18a, miR-18b, miR-19b, miR-31, miR-126, miR-142-3p, miR-133b, miR-144, miR-195, miR-223, miR-451 and miR-497 was identified with an intermediate expression level in osteosarcoma clinical samples compared to osteoblasts and bone, which may reflect the differentiation level of osteosarcoma relative to the undifferentiated osteoblast and fully differentiated normal bone. Significance: This study provides an integrated analysis of miRNA and mRNA in osteosarcoma, and gives new insight into the complex genetic mechanisms of osteosarcoma development and progression.

Demethylation of microRNA-142 induced by demethylation agents plays a suppressive role in osteosarcoma cells

“…Although previous data demonstrated that miR-142 was downregulated in OS cell lines, as detected by global microarray analyses (17), the role of miR-142 in OS remains unknown.…”

“…Although miR-142 has been found to be downregulated in OS cell lines (17), the role and epigenetic mechanisms of miR-142 in OS remain unknown. The aim of the present study was to compare the expression of miR-142 between OS and pericancerous tissues and investigate the role of epigenetic regulation in the decreased expression of miR-142 in OS.…”

Serum miR-9 as a prognostic biomarker in patients with osteosarcoma

“…29 The molecular mechanisms underlying miR-9 and the regulation of osteosarcoma carcinogenesis remain unclear and require further study.…”

Upregulation of microRNA-17-92 cluster associates with tumor progression and prognosis in osteosarcoma

“…The miR-17-92 cluster composed of seven miRNAs (miR-17-5p, miR-17-3p, miR-18a, miR-19a, miR-20a, miR-19b, and miR-92-1) [16,17]. Recent studies have observed that the miR-17-92 cluster is overexpressed in several types of cancer [18][19][20]. Studies also have shown that overexpression of miR-17-92 cluster may regulate cell cycle, apoptosis, invasion, and proliferation in many types of human cancer [21,22].…”