MicroRNA-mediated gene regulations in human sarcomas
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Cellular and Molecular Life Sciences
MULTI-AUTHOR REVIEW
MicroRNA-mediated gene regulations in human sarcomas Subbaya Subramanian • Reena V. Kartha
Received: 8 August 2012 / Revised: 9 August 2012 / Accepted: 9 August 2012 Ó Springer Basel AG 2012
Abstract Sarcomas are a heterogeneous group of tumors with mesenchymal origins. Sarcomas are broadly classified into bone and soft tissue sarcomas with over 50 subtypes. Despite recent advances in sarcoma classification and treatment strategies, the prognosis of some aggressive sarcoma types remains poor due to treatment infectiveness and development of drug resistance. A better understanding of sarcoma pathobiology will significantly increase the potential for the development of therapeutics and treatment strategies. Recently, expressions of microRNAs (miRNA), a class of small non-coding RNAs, have been found to be deregulated in many sarcomas and are implicated in sarcoma pathobiology. Comprehensive understanding of gene regulatory networks mediated by miRNAs in each sarcoma type and the conservation of some shared/conserved miRNA-gene networks could be potentially investigated in the prevention, diagnosis, prognosis and as multi-modal treatment options in these cancers. In this review, we will discuss the current knowledge of miRNA–gene regulatory networks in various sarcoma types and give a perspective of the complex multilayer miRNA-mediated gene regulation in sarcomas.
S. Subramanian (&) Department of Surgery, University of Minnesota, 11-212 Moos Tower (Mail Code: MMC 195), 515 Delaware St, S.E, Minneapolis, MN 55455, USA e-mail: [email protected] S. Subramanian Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA R. V. Kartha Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN 55455, USA
Keywords Sarcoma MicroRNA Soft tissue sarcoma Bone sarcoma Markers Expression Gene networks Osteosarcoma Rhabdomyosarcoma MPNSTs GIST Synovial sarcoma Liposarcoma
Introduction Sarcomas are mesenchymal tumors that accounts for about 1 % of all malignant tumor types in humans [1]. Approximately 15 % of all malignant tumors in children are pediatric sarcomas. Sarcomas can occur anywhere in the body, but the majority occur in the extremities and can be broadly classified into bone and soft tissue sarcoma with over 50 subtypes [2, 3]. Sarcoma nomenclature is generally based on the cell and/or tissue type, as in osteosarcoma (OS), angiosarcoma, rhabdomyosarcoma (RMS) and liposarcoma. Even within a specific sarcoma type, tumors are highly heterogeneous and the histopathological and clinical features are not always distinct, causing a diagnostic challenge. Several sarcoma types, however, are characterized by chromosomal translocations resulting in tumorspecific fusion transcripts [4, 5]. The presence or absence of such fusion transcripts are widely used as diagnostic markers for certain subtypes [6]. In addition, DNA copy number changes are used in sarcoma diagnosis [7]. Despite these markers, a si
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