title: [Expression and significance of microRNAs in the p53 pathway in ovarian cancer cells and serous ovarian cancer tissues].
abstract: OBJECTIVE
  The aim of this study was to investigate whether miR-449a, miR-449b and miR-192 family microRNAs play the same roles in p53 pathway as miR-34 family in ovarian cancer.
  
  
  METHODS
  Wild-type p53 ovarian carcinoma cell line A2780 cells were treated with genotoxic agent adriamycin. The reactivation of p53 was detected by Western blot. The expression of miR-449a/b, miR-34a, miR-34b, miR-34c, miR-192 and miR-194 were detected by real-time quantitative PCR. Mutant p53 ovarian cancer cell line SKOV3.ipl cells were transfected with pre-microRNAs and the cell-cycle changes were detected. The expression level of miR-449a/b, miR-34a, miR-34b, miR-34c, miR-192 and miR-194 in serous ovarian carcinomas of varying grade and stage were compared with real-time PCR.
  
  
  RESULTS
  The expressions of miR-449a/b, miR-34b and miR-34c were 19-fold to 21-fold elevated after p53 activation by genotoxic agent. Ectopic expression of miR-449b, as well as miR-34c, resulted in cell-cycle arrest in SKOV3.ipl cells. The expression of miR-449a/b was parallel with that of miR-34b, miR-34c, and were significantly lower in late stage and high-grade serous carcinomas than in the normal fallopian tube, early stage and low-grade serous carcinomas. The expression of miR-192, miR-194 and miR-34a did not show evident features in serous ovarian carcinomas and were much lower than miR-449a/b, miR-34b and miR-34c in normal fallopian tube.
  
  
  CONCLUSIONS
  As tumor-suppressor microRNAs, miR-449a/b, miR-34b and miR-34c cooperate and play important roles in p53 pathway. Their inactivation may contribute to the carcinogenesis and progression of serous ovarian carcinomas.
authors.affiliation: Institute of Clinical Molecular Biology, Peking University People's Hospital, Beijing 100044, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.forename: Xiang-jun
authors.initials: XJ
authors.lastname: He
authors.forename: Li-ping
authors.initials: LP
authors.lastname: Ma
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.forename: Ye-xia
authors.initials: YX
authors.lastname: Cheng
authors.forename: Heng
authors.initials: H
authors.lastname: Cui
mesh_terms: D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D002453:Cell Cycle; D045744:Cell Line, Tumor; D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004317:Doxorubicin / Q000494:pharmacology; D005260:Female; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D000903:Antibiotics, Antineoplastic; D035683:MicroRNAs; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D004317:Doxorubicin