MicroRNA-27a Contributes to Rhabdomyosarcoma Cell Proliferation by Suppressing RARA and RXRA.
BACKGROUND
Rhabdomyosarcomas (RMS) are rare but very aggressive childhood tumors that arise as a consequence of a regulatory disruption in the growth and differentiation pathways of myogenic precursor cells. According to morphological criteria, there are two major RMS subtypes: embryonal RMS (ERMS) and alveolar RMS (ARMS) with the latter showing greater aggressiveness and metastatic potential with respect to the former. Efforts to unravel the complex molecular mechanisms underlying RMS pathogenesis and progression have revealed that microRNAs (miRNAs) play a key role in tumorigenesis.


RESULTS
The expression profiles of 8 different RMS cell lines were analyzed to investigate the involvement of miRNAs in RMS. The miRNA population from each cell line was compared to a reference sample consisting of a balanced pool of total RNA extracted from those 8 cell lines. Sixteen miRNAs whose expression discriminates between translocation-positive ARMS and negative RMS were identified. Attention was focused on the role of miR-27a that is up-regulated in the more aggressive RMS cell lines (translocation-positive ARMS) in which it probably acts as an oncogene. MiR-27a overexpressing cells showed a significant increase in their proliferation rate that was paralleled by a decrease in the number of cells in the G1 phase of the cell cycle. It was possible to demonstrate that miR-27a is implicated in cell cycle control by targeting the retinoic acid alpha receptor (RARA) and retinoic X receptor alpha (RXRA).


CONCLUSIONS
Study results have demonstrated that miRNA expression signature profiling can be used to classify different RMS subtypes and suggest that miR-27a may have a therapeutic potential in RMS by modulating the expression of retinoic acid receptors.
Department of Biology, University of Padova, Padova, Italy; C.R.I.B.I.-Biotechnology Centre, University of Padova, Padova, Italy.
Lucia
L
Tombolan
Department of Biology, University of Padova, Padova, Italy; C.R.I.B.I.-Biotechnology Centre, University of Padova, Padova, Italy.
Matteo
M
Zampini
C.R.I.B.I.-Biotechnology Centre, University of Padova, Padova, Italy.
Silvia
S
Casara
Department of Biology, University of Padova, Padova, Italy; C.R.I.B.I.-Biotechnology Centre, University of Padova, Padova, Italy.
Elena
E
Boldrin
Institute of Pediatric Research, IRP, Padova, Italy; Department of Women's and Children's Health, Oncohematology Unit, University of Padova, Padova, Italy.
Angelica
A
Zin
Department of Women's and Children's Health, Oncohematology Unit, University of Padova, Padova, Italy.
Gianni
G
Bisogno
Department of Women's and Children's Health, Oncohematology Unit, University of Padova, Padova, Italy.
Angelo
A
Rosolen
Department of Biology, University of Padova, Padova, Italy.
Cristiano
C
De Pittà
Department of Biology, University of Padova, Padova, Italy; C.R.I.B.I.-Biotechnology Centre, University of Padova, Padova, Italy.
Gerolamo
G
Lanfranchi
D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology*; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D057809:HEK293 Cells; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D018168:Receptors, Retinoic Acid / Q000502:physiology*; D000072482:Retinoic Acid Receptor alpha; D047490:Retinoid X Receptor alpha / Q000502:physiology*; D012208:Rhabdomyosarcoma / Q000503:physiopathology*
C531388:MIRN27 microRNA, human; D035683:MicroRNAs; C000607071:RARA protein, human; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D047490:Retinoid X Receptor alpha