Genomic imbalances are involved in miR-30c and let-7a deregulation in ovarian tumors: implications for HMGA2 expression
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Antonio Agostini1,2, Marta Brunetti1,2, Ben Davidson3,4, Claes G. Tropé5, Sverre Heim1,2,4, Ioannis Panagopoulos1,2, Francesca Micci1,2
1Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
2Centre for Cancer Biomedicine, University of Oslo, Oslo, Norway
3Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
4Faculty of Medicine, University of Oslo, Oslo, Norway
5Department of Gynecology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
Francesca Micci, email: [email protected]
Keywords: HMGA2, miR-30c, let-7a, FHIT, LIN28A
Received: July 05, 2016 Accepted: January 31, 2017 Published: March 01, 2017
The High-mobility group AT-hook 2 protein (HMGA2) is involved in different processes during tumorigenesis. High expression levels of HMGA2 are found in various types of cancer, with recent studies highlighting the important role of miRNAs in the regulation of HMGA2 expression. We report a study of 155 ovarian tumors (30 sex-cord stromal tumors, 22 borderline tumors, and 103 carcinomas) analyzed for HMGA2 expression as well as the expression of two miRNAs targeting this gene, let-7a and miR-30c. We also evaluated the expression of the fragile histidine triad (FHIT) and lin28 homologues (LIN28A/B) genes which are known to be an enhancer of miR-30c expression and a repressor of let-7a, respectively. HMGA2 was found expressed at high levels in most samples analyzed, with clear cell carcinomas as the only exception. let-7a and miR-30c were highly deregulated in all tumor types. LIN28A and FHIT were found overexpressed in all examined tumor types. The chromosomal imbalances that might lead to loss of the genes expressing let-7a and miR-30c could be evaluated on the basis of previously generated karyotypic and high resolution comparative genomic hybridization (CGH) data on 103 tumors. 76% of the samples with an imbalanced genome had at least one chromosomal aberration leading to a deletion of a miRNA cluster for let-7a and miR-30c. FISH using locus specific probes for these clusters validate the aberrations at the gene level. Our study shows that genomic imbalances are involved in miR-30c and let-7a deregulation. One can reasonably assume that dysregulation of these miRNAs is a cause leading to HMGA2 upregulation in ovarian tumors.
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