MicroRNAs and epigenetic mechanisms of rhabdomyosarcoma development.
Rhabdomyosarcoma is the most common type of soft tissue sarcoma in children. Two main subtypes of rhabdomyosarcoma with different molecular pattern and distinct clinical behaviour may be identified - embryonal and alveolar rhabdomyosarcoma. All types of rhabdomyosarcoma are believed to be of myogenic origin as they express high levels of myogenesis-related factors. They all, however, fail to undergo a terminal differentiation which results in tumour formation. In the aberrant regulation of myogenesis in rhabdomyosarcoma, microRNAs and epigenetic factors are particularly involved. Indeed, these mediators seem to be even more significant for the development of rhabdomyosarcoma than canonical myogenic transcription factors like MyoD, a master regulatory switch for myogenesis. Therefore, in this review we focus on the regulation of rhabdomyosarcoma progression by microRNAs, and especially on microRNAs of the myo-miRNAs family (miR-1, -133a/b and -206), other well-known myogenic regulators like miR-29, and on microRNAs recently recognized to play a role in the differentiation of rhabdomyosarcoma, such as miR-450b-5p or miR-203. We also review changes in epigenetic modifiers associated with rhabdomyosarcoma, namely histone deacetylases and methyltransferases, especially from the Polycomp Group, like Yin Yang1 and Enhancer of Zeste Homolog2. Finally, we summarize how the functioning of these molecules can be affected by oxidative stress and how antioxidative enzymes can influence the development of this tumour. This article is part of a Directed Issue entitled: Rare Cancers.
Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Gronostajowa 7, 30-387 Krakow, Poland.
Maciej
M
Cieśla
Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Gronostajowa 7, 30-387 Krakow, Poland. Electronic address: jozef.dulak@uj.edu.pl.
Józef
J
Dulak
Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Gronostajowa 7, 30-387 Krakow, Poland. Electronic address: alicja.jozkowicz@uj.edu.pl.
Alicja
A
Józkowicz
D063646:Carcinogenesis / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics; D044127:Epigenesis, Genetic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D024510:Muscle Development; D017570:MyoD Protein / Q000235:genetics; D018384:Oxidative Stress; D012208:Rhabdomyosarcoma / Q000235:genetics* / Q000473:pathology
D035683:MicroRNAs; D017570:MyoD Protein
Epigenetic modifications; Heme oxygenase-1; Oxidative stress; Rhabdomyosarcoma; microRNAs