Molecular bases of aberrant miR‐182 expression in ovarian cancer

Abstract

The molecular bases of miR-182 deregulation in epithelial ovarian cancers (EOCs) remain unknown and its diagnostic or prognostic role in EOCs is still unclear. We performed miR-182 expression analysis using a microarray approach and real-time PCR (qPCR). We also used array comparative genomic hybridization and methylated DNA immunoprecipitation to study copy number changes and methylation aberrations within coding locus/promoter sequences of miR-182 in EOC tissues, respectively. We have found that miR-182 expression is significantly increased in EOC (P < 0.00001) and that higher miR-182 expression in EOC is linked with significantly shorter overall survival (P = 0.026). The methylation of miR-182 promoter was significantly associated with lower miR-182 expression in EOC tissues (P = 0.045). miR-182 over-expression is connected with copy number (CN) gains of this miRNA coding sequences in EOC (P = 0.002), and the number of PRDM5 copies is significantly and inversely correlated with miR-182 expression evaluated by qPCR (R = -0.615, P = 0.009). We conclude that the aberrant miR-182 expression in EOC may be due to CN gains within its coding locus. The miR-182 promoter is rarely methylated in EOC, and its methylation status is associated with lower miR-182 expression. Deletion of the PRDM5 locus may play a supportive role in miR-182 overexpression in EOC. miR-182 is an unfavorable prognostic factor in EOC. © 2016 Wiley Periodicals, Inc.

Multifaceted Role of PRDM Proteins in Human Cancer

“…Overall, these data suggest that PRDM5 is a tumor suppressor in several human cancer types where it could represent a molecular marker for diagnosis and prognosis and a promising target for their therapy. Accordingly, this concept is also supported by a study in which repression of PRDM5 function, due to deletions in its locus along with miR-182 sequence amplification, was shown to play a co-operative role in ovarian cancers [141]. Finally, epigenome and transcriptome profiling of mouse primary liver cancer identified Tbx3 and Prdm5 as major microenvironment-dependent and epigenetically regulated lineage-commitment factors, a function that is conserved in humans [142].…”

Combined measurement of miRNA-183, HE4, and CA-125 increases diagnostic efficiency for ovarian cancer

“…Real-time quantitative PCR was performed using a strata-gene Mx3005p. U6 served as an internal reference, and the Ct value was used for calculation of the relative expression of target genes with the 2 -Ct method [7][8][9].…”

“…The present results also showed high expression of miR-205 in the plasma of ovarian cancer patients, suggesting that miR-205 acts as an oncogene in ovarian cancer, which is consistent with a previous report. [8] A study involving whole genomic miRNA screening [9] showed that miR-183 expression is markedly up-regulated in ovarian cancer compared to normal ovarian tissues, suggesting that miR-183 is involved in the progression of ovarian cancer. Another study [10] used qRT-PCR for the detection of serum miR183.…”

“…Indeed, there are stable miRNAs in the plasma which may serve as new biomarkers for cancers [5,6]. Studies [7][8][9][10][11][12] have shown that the expression of miR-205, miR-182, and miR-183 in the peripheral blood increases significantly in ovarian cancer patients, but whether or not these miRNAs can serve as effective biomarkers of ovarian cancer is not clear. In the present study, qRT-PCR was used to detect serum miRNA, CA-125, and HE4 in ovarian cancer patients and healthy controls, and evaluate the clinical significance of miRNA, CA-125, and HE4 in the diagnosis of ovarian cancer.…”

MicroRNA como potencial biomarcador prognóstico e preditivo de resposta à quimioterapia baseada em platina em pacientes portadoras de câncer de ovário: revisão sistemática da literatura com meta-análise em sobrevida global

“…Enquanto, os membros da família miR-200 são considerados supressores tumorais, a maioria dos estudos realizados relacionaram a superexpressão com o câncer de ovário [217] . Entretanto, alguns estudos relataram os membros da família miR-200 como reduzidos [217] ou sequer alterados no câncer de ovário [218] . Estes resultados opostos podem ser devidos a diferentes controles ou inclusão de células de estroma com falta de expressão de miRNAs.…”