Expression and significance of microRNAs in the p53 pathway in ovarian cancer cells and serous ovarian cancer tissues

TLDR: As tumor-suppressor microRNAs,miR-449a/b, miR-34b and mi-34c cooperate and play important roles in p53 pathway and may contribute to the carcinogenesis and progression of serous ovarian carcinomas.

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. Key words: MicroRNA ;  P53 pathway;  Ovarian neoplasms