| Summary: | 碩士 === 國立成功大學 === 臨床醫學研究所 === 101 === Ovarian cancer is the ninth leading cause of global cancer-related deaths. It is associated with high mortality due to high recurrence rates, especially metastatic recurrence. Metastatic recurrence is the main feature of advanced ovarian cancer and a direct cause of death. It is important to identify biomarkers and therapeutic targets for early detection and treatment of metastatic recurrence of ovarian cancer. The focus of our study is on microRNAs (miRNAs), which are small (~22 nt) non-coding RNAs that negatively regulate downstream target genes. They control a wide range of biological functions and their abnormal expression may cause cancer. Thus, we hypothesized that microRNA dysregulation are involved in the recurrence of ovarian cancer. We used microarrays to analyze global microRNA expression in the primary and recurrent tumors of 2 patients. We found that microRNA-150 was upregulated in recurrent tumors in comparison to primary tumors. To verify the relationship between miR-150 expression and cancer recurrence in ovarian cancer, we collected primary and recurrent tumors from 22 clinical patients. miR-150 was upregulated in 16 of these patients. Analysis of 2 Gene Expression Omnibus databases revealed a positive association between miR-150, shorter survival time, and early recurrence. Next, we explored the function of miR-150 in ovarian cancer recurrence in vitro. Expression of miR-150 positively correlated with cell migration; overexpression of miR-150 in BG-1 ovarian cancer cells promoted migration and invasion but did not influence proliferation. In contrast, inhibition of miR-150 in SKOV3 reduced cell migration and invasion. To identify the target genes of miR-150-mediated invasion and migration, we used whole gene expression microarrays. Expression signatures were analyzed with 5 microRNA target prediction software programs, which identified MYB (v-myb myeloblastosis viral oncogene homolog) as a target of miR-150 regulation that is also associated with cell motility and invasion. These results suggest miR-150 upregulation mediates the progression of metastatic recurrence of ovarian cancer. miR-150 promotes tumor cell invasion and migration by targeting the MYB pathway. In the future, we will directly examine the function of miR-150 in metastasis in vivo.
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