MicroRNA expression signature of human sarcomas

Subramanian, Subbaya; Lui, Weng‐Onn; Lee, C. H.; Espinosa, Íñigo; Nielsen, Torsten O.; Heinrich, Michael C.; Corless, C. L.; Fire, Andrew; Rijn, Matt van de

doi:10.1038/sj.onc.1210836

Cited by 214 publications

(211 citation statements)

References 29 publications

(29 reference statements)

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“…Of note, dysregulation of miR-16, miR-195 and miR-497 have also been found in a range of other cancers, including chronic lymphocytic leukaemia, prostate, pancreas, cervical carcinomas together with sarcomas and benign uterine leiomyomata (Table 4). 12,[53][54][55][56][57][58][59][60][61][62][63] Little is known about the mechanisms of micro-RNA deregulation in neoplastic tissue. MicroRNA genes are commonly located at minimal regions of amplification, loss of heterozygosity and breakpoint regions, suggesting that abnormal microRNA profiles can be caused by somatic gene mutation.…”

Section: Discussionmentioning

confidence: 99%

Potentially important microRNA cluster on chromosome 17p13.1 in primary peritoneal carcinoma

et al. 2009

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MicroRNAs are a group of small non-coding RNAs approximately 22 nucleotides in length. Recent work has shown differential expression of mature microRNAs in human cancers. We characterized the alteration in expression of a select group of microRNAs in primary peritoneal carcinoma relative to matched cases of ovarian serous carcinoma. MicroRNA expression was analysed using semi-quantitative stem-loop RT-PCR on a set of 34 formalin-fixed paraffin-embedded samples. Protein expression of p53 and bcl-2 was quantified in the corresponding tissue microarray. We provide definitive evidence that there is downregulation of a select group of microRNAs in tumours meeting Gynaecological Oncology Group criteria for primary peritoneal carcinoma relative to ovarian serous carcinoma. Specifically, we show decreased p53 expression and downregulation of miR-195 and miR-497 from the microRNA cluster site at chromosome 17p13.1 in primary peritoneal carcinoma relative to ovarian serous carcinoma. miR-195 and miR-497 may have potential roles as tumour-suppressor genes in primary peritoneal tumourigenesis.

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Section: Discussionmentioning

confidence: 99%

Potentially important microRNA cluster on chromosome 17p13.1 in primary peritoneal carcinoma

et al. 2009

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“…To further explore the relevance of this finding, we compared our findings with other published works on miRNA expression profile in rhabdomyosarcoma and compiled expression data for miR-1, miR-133a, miR-133b, and miR-206 from ten studies that compared rhabdomyosarcoma with normal skeletal muscle (Supplementary Table 2). [9][10][11][12][13][24][25][26][27][28] The prior studies showed underexpression of miR-1 and miR-133a (if examined) in all nine studies and variable expression of miR-133b and miR-206 across the comparisons of rhabdomyosarcoma to normal skeletal muscle. The underexpression of the myomiRs miR-1, miR-133a, and miR-206 in well-differentiated liposarcoma was validated using qRT-PCR (Figures 2b and d).…”

Section: Qrt-pcr Analysismentioning

confidence: 99%

“…For example, we and others found that the tumor suppressor miR-29 was found to be downregulated in rhabdomyosarcoma. 9,10 Results identified a regulatory circuit involving miR-29, NF-κB, and YY1 that appears to be dysregulated in rhabdomyosarcoma and might contribute to the dedifferentiation phenotype of these tumors. 9 Re-expression of miR-29 in xenograft tumors and rhabdomyosarcoma cell lines led to inhibition of tumor proliferation as well as stimulation of myogenic differentiation.…”

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confidence: 99%

A selective screening platform reveals unique global expression patterns of microRNAs in a cohort of human soft-tissue sarcomas

Balkhi

Ladner

et al. 2016

Laboratory Investigation

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Sarcomas are malignant heterogenous tumors of mesenchymal derivation. Emerging data suggest that miRNA might have a causal role in sarcomagenesis. Herein, we used a selective miRNA screening platform to study the comparative global miRNA expression signatures in a cohort of human sarcomas with the caveat that comparisons between tumor and non-tumor cells were performed from the same patients using formalin-fixed paraffin-embedded tissue. Five histologic types were examined that included: myxoid liposarcoma, well-differentiated liposarcoma, dedifferentiated liposarcoma, pleomorphic rhabdomyosarcoma, and synovial sarcoma. In addition, soft-tissue lipomas and normal fat were included as a separate set of controls for the lipogenic tumors. Clustering analysis showed a distinct global difference in expression patterns between the normal and sarcoma tissues. Expression signatures in an unsupervised hierarchical clustering analysis revealed tight clustering in synovial and myxoid liposarcomas, and the least clustering was observed in the pleomorphic rhabdomyosarcoma subtype. MiR-145 showed underexpression in pleomorphic rhabdomyosarcoma, well-differentiated liposarcoma, and synovial sarcoma. Unexpectedly, we found that a set of muscle-specific microRNAs (miRNAs; myomiRs): miR-133, miR-1, and miR-206 was significantly underexpressed in well-differentiated liposarcoma and synovial sarcoma, suggesting that they may function as tumor suppressors as described in muscle-relevant rhabdomyosarcomas. In addition, a tight linear progression of miRNA expression was identified from normal fat to dedifferentiated liposarcoma. These results suggest that miRNA expression profiles could elucidate classes of miRNAs that may elicit tumor-relevant activities in specific sarcoma subtypes. Sarcomas are rare malignant heterogeneous tumors of mesenchymal derivation with over 50 histologic types described. 1 The pathogenesis and biology of many of the different histologic subtypes remain poorly understood. Recent progress in understanding the biology of sarcomas has identified distinct molecular and pathologic entities within these heterogeneous groups of tumors that have paved the way for development of targeted therapies. There are emerging data that seem to suggest that miRNA might be a driver in sarcomagenesis with potential therapeutic implications. microRNAs (miRNAs) are non-coding strands of RNA of 22 nucleotides in length that regulate the expression of genes involved in processes such as development, differentiation, cell proliferation, metabolism, cell death, viral infection, and cancer. 2,3 They have a broad effect through base pairing with mRNA at their 3′ untranslated region to inhibit translation or to target the mRNA for degradation. Bioinformatics predictions have shown that miRNAs regulatẽ 30% of mammalian protein-coding genes. Their role in the molecular biology of cancers is well-established partly

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“…[9][10][11][12][13] However, there is no comprehensive expression analysis that catalogs miRNA expression patterns in the wide variety of existing sarcoma types with sufficient sample size to carry statistical power. In our earlier studies, we have reported preliminary analysis of miRNA expression levels in a small series of sarcomas 14 as well as in colon cancer. 15 Exhaustive analysis of miRNA expression patterns in sarcomas will accelerate the identification and development of novel miRNA-based biomarkers for these tumors.…”

mentioning

confidence: 99%