Analysis of miRNA-gene expression-genomic profiles reveals complex mechanisms of microRNA deregulation in osteosarcoma

Maire, Georges; Martin, Jeff W.; Yoshimoto, Maisa; Chilton‐MacNeill, Susan; Zieleńska, Maria; Squire, Jeremy A.

doi:10.1016/j.cancergen.2010.12.012

Cited by 122 publications

(115 citation statements)

References 56 publications

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“…At the molecular level, the majority of OSs exhibit complex genomic aberrations and highly variable patterns of gene expression. Emerging evidence has demonstrated that several miRNAs were altered in OS, some of which play a critical role in carcinogenesis (6,10,19,20). Detailed understanding of miRNAs and their regulation mechanisms may aid the development of novel strategies to improve OS treatment.…”

Section: Discussionmentioning

confidence: 99%

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

Ding¹,

Hu²,

Ni³

et al. 2015

Oncology Letters

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Abstract. Osteosarcoma (OS), the most common malignant bone tumor, occurs mainly in adolescents and young adults, with a morbidity of ~5 cases per million. The expression levels of microRNAs (miRNAs) as tumor suppressors were recently found to be downregulated in OS. Certain alterations of miRNAs and the possible mechanisms through which miRNAs affect cell proliferation and migration in OS were recently found to be correlated with methylation epigenetic mechanisms. In this study, it was demonstrated that, due to hypermethylation, the expression level of miRNA-142 (miR-142) was significantly downregulated in OS tissues and cells compared with that in control samples. The present study demonstrated an increased expression of miR-142 in Saos-2 and MG63 cells treated with demethylation agents, suggesting that the effect of such agents on cell growth, inhibition of invasion and cell cycle retardation may be mediated by miR-142 in OS.

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Section: Discussionmentioning

confidence: 99%

“…miRNAs are short endogenous non-coding RNAs that post-transcriptionally regulate the expression of target genes (oncogenes or tumor suppressor genes) involved in several types of cancer, including OS (6). A single miRNA may silence a large number of genes, allowing these molecules extensive control over numerous cellular functions (7).…”

Section: Introductionmentioning

confidence: 99%

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

Ding¹,

Hu²,

Ni³

et al. 2015

Oncology Letters

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show abstract

“…In the present study, it was suggested that SMAD4 is a direct target of miR-574-3p and the associated genes CDKN1A, CDKN2B as well as ID3 were strongly suppressed by miR-574-3p transfection. SMAD4 is often mutated in numerous cancers and it acts as a tumor suppressor that is involved in the regulation of the TGF-β signal transduction pathway, which negatively regulates growth of epithelial cells and the extracellular matrix (28)(29)(30)(31). Therefore, the inhibition of SMAD4 and its downstream proteins may be an important part of the mechanism of miR-574-3p in osteosarcoma.…”

Section: Downregulation Of Mir-574-3p Inhibited Cell Growth and Inducmentioning

confidence: 99%

miR-574-3p acts as a tumor promoter in osteosarcoma by targeting SMAD4 signaling pathway

Liu

Zhou

et al. 2016

Oncology Letters

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Abstract. Human osteosarcoma is the most common primary bone malignancy sarcoma that affects primarily children and people <20 years old. In the present study, it was demonstrated that miR-574-3p was downregulated in human osteosarcoma U2OS, SAOS and MG63 cells lines as well as in osteosarcoma tissue compared with the normal tissues. Downregulation of miR-574-3p by antisense miR-574-3p, inhibited cell growth and induced cell apoptosis. Overexpression of miR-574-3p by transfection with miR-574-3p mimics promoted the growth of U2OS cells. The present study then identified mothers against decapentaplegic homolog 4 (SMAD4) as a target of miR-574-3p and SMAD4 was suppressed in miR-574-3p transfected cells. Overexpression of SMAD4 could rescue the promoting effects of miR-574-3p on cancer cell growth. In conclusion, miR-574-3p exerts tumor-promoting roles by targeting the tumor-suppressing gene SMAD4 and its downstream signaling in human osteosarcoma, which provides a novel target for the treatment.

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“…In the present study, the expression levels of the six members of miR-17-92 cluster in MG-63, Saos-2, U2-OS and hFOB 1.19 cells were detected by fluorescence quantitative RT-PCR, finding that miR-17, miR-19b, miR-20a and miR-19a were remarkably up-regulated in osteosarcoma cells. Differently, previous study found that the expression of the members of miR-17-92 cluster was not changed in human osteosarcoma clinical samples assessed by miRNA microarray [21]. As the lack of researching on miR-19b functions in osteosarcoma cells, miR-19b is selected for the further investigations.…”

Section: Discussionmentioning

confidence: 92%

“…Current studies suggest that miRNA exerts extensive gene regulation functions from all levels of gene activities, being involved in a series of biological processes such as embryonic development, cell proliferation, cell apoptosis and energy metabolism [17][18][19]. Researches have found that biological behaviors of osteosarcoma closely related to certain miRNA family members in the occurrence and development process [20,21].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-19b targets Mfn1 to inhibit Mfn1-induced apoptosis in osteosarcoma cells

Li¹,

Wang²,

Wu³

et al. 2014

neo

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Accumulative evidence has confirmed that, miR-17-92, a typical polycistronic mRNA cluster, was up-regulated in various solid tumors, and play an important role in the occurrence and development progress of tumors. In our study, we detected the six members of miR-17-92 cluster in osteosarcoma cell line, finding that the expression of miR-17 and miR-19b was up-regulated significantly. Further studies have found that Mfn1 was one of the target genes of miR-19b and the transcription and expression level of Mfn1 were down-regulated by miR-19b. MTS, flow cytometry, TUNEL-DAPI, Annexin V-FITC and transwell assay demonstrated that Mfn1 significantly blocked the cell cycle, promoted apoptosis and inhibited proliferation and invasion of osteosarcoma cells. Whereas, miR-19b targets 3'UTR sequences of Mfn1 genes inhibit the expression of Mfn1, thus inhibited Mfn1 triggered anti-cancer effect. Taken together, miR-19b functions by targeting Mfn1 reduce the protein expression level, thus provides a novel target to understand the molecular biology and genetics mechanisms of occurrence and development of osteosarcoma, contributing to the diagnosis and therapy of osteosarcoma.

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Analysis of miRNA-gene expression-genomic profiles reveals complex mechanisms of microRNA deregulation in osteosarcoma

Cited by 122 publications

References 56 publications

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

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

miR-574-3p acts as a tumor promoter in osteosarcoma by targeting SMAD4 signaling pathway

MicroRNA-19b targets Mfn1 to inhibit Mfn1-induced apoptosis in osteosarcoma cells

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