A differentiation-based microRNA signature identifies leiomyosarcoma as a mesenchymal stem cell-related malignancy Journal Article

Authors: Danielson, L. S.; Menendez, S.; Attolini, C. S. O.; Guijarro, M. V.; Bisogna, M.; Wei, J.; Socci, N. D.; Levine, D. A.; Michor, F.; Hernando, E.
Article Title: A differentiation-based microRNA signature identifies leiomyosarcoma as a mesenchymal stem cell-related malignancy
Abstract: Smooth muscle (SM) is a spontaneously contractile tissue that provides physical support and function to organs such as the uterus. Uterine smooth muscle- related neoplasia comprise common well-differentiated benign lesions called leiomyomas (ULM), and rare, highly aggressive and pleomorphic tumors named leiomyosarcomas (ULMS). MicroRNAs (miRNAs) are small non-coding RNAs that play essential roles in normal cellular development and tissue homeostasis that can be used to accurately subclassify different tumor types. Here, we demonstrate that miRNAs are required for full smooth muscle cell (SMC) differentiation of bone marrow-derived human mesenchymal stem cells (hMSCs). We also report a miRNA signature associated with this process. Moreover, we show that this signature, along with miRNA profiles for ULMS and ULM, are able to subclassify tumors of smooth muscle origin along SM differentiation. Using multiple computational analyses, we determined that ULMS are more similar to hMSCs as opposed to ULM, which are linked with more mature SMCs and myometrium. Furthermore, a comparison of the SM differentiation and ULMS miRNA signatures identified miRNAs strictly associated with SM maturation or transformation, as well as those modulated in both processes indicating a possible dual role. These results support separate origins and/or divergent transformation pathways for ULM and ULMS, resulting in drastically different states of differentiation. In summary, this work expands on our knowledge of the regulation of SM differentiation and sarcoma pathogenesis. Copyright © American Society for Investigative Pathology.
Keywords: human tissue; human cell; smooth muscle fiber; microrna; cluster analysis; cell maturation; cell differentiation; cell transformation, neoplastic; cell transformation; mesenchymal stem cell; leiomyosarcoma; micrornas; uterine neoplasms; muscle, smooth; mesenchymal stem cells; phylogeny; myometrium; smooth muscle tumor
Journal Title: American Journal of Pathology
Volume: 177
Issue: 2
ISSN: 0002-9440
Publisher: Elsevier Science, Inc.  
Date Published: 2010-08-01
Start Page: 908
End Page: 917
Language: English
DOI: 10.2353/ajpath.2010.091150
PUBMED: 20558575
PROVIDER: scopus
PMCID: PMC2913343
Notes: --- - "Cited By (since 1996): 2" - "Export Date: 20 April 2011" - "CODEN: AJPAA" - "Source: Scopus"
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