Expression analysis of MIR182 and its associated target genes in advanced ovarian carcinoma.
BRCA1/BRCA2 mutations are common and the hallmarks of high-grade serous ovarian carcinoma. We found that MIR182, a negative BRCA1 regulator, is significantly overexpressed in high-grade serous ovarian carcinoma. To examine whether overexpression of MIR182 and its target genes, including BRCA1, HMGA2 (high-mobility group A2), FOXO3 and MTSS1, are associated with high-grade serous ovarian carcinoma tumor types and clinical outcome, we studied MIR182 by in situ hybridization and its target gene expression by immunohistochemistry in 117 cases of advanced ovarian cancer. We found that high-grade serous ovarian carcinoma had significantly higher MIR182 (P=0.0003) and HMGA2 (P=0.04) expression, and significantly lower BRCA1 (P<0.0001) and FOXO3 (P<0.001) expression than normal controls. MIR182 is significantly correlated with MTSS1 expression (r=0.31; P<0.001), whereas other target genes did not show a significant correlation with MIR182, indicating a complicated regulatory mechanisms of these genes in high-grade serous ovarian carcinoma. Among the examined MIR182 target genes, only HMGA2 was significantly associated with serous type carcinomas (P<0.01), ascites (P<0.01) and high death rate (P=0.02). FOXO3 expression was associated with lower-stage disease (P=0.04) and solid growth pattern (P=0.03). MIR182 expression is significantly higher in high-grade serous ovarian carcinoma than in fallopian tubes.
Department of Pathology, Northwestern University, Feinberg Medical School, Chicago, IL, USA.
Brian D
BD
McMillen
Margarita M
MM
Aponte
Zhaojian
Z
Liu
Irene B
IB
Helenowski
Denise M
DM
Scholtens
Barbara M
BM
Buttin
Jian-Jun
JJ
Wei
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018284:Cystadenocarcinoma, Serous / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000556:secondary; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D025743:HMGA2 Protein / Q000235:genetics; D006801:Humans; D007087:Illinois / Q000453:epidemiology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008198:Lymph Nodes / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D015996:Survival Rate
D004273:DNA, Neoplasm; D025743:HMGA2 Protein; D035683:MicroRNAs; C538984:Mirn182 microRNA, human