Expression And Role Of Mir-100 In Ovarian Cancer

Ovarian cancer is the most common and the leading cause of death from gynecological malignancy. The 5-year survival rate of advanced ovarian cancer is only 20%-30%. The symptoms of ovarian cancer are generally observed only after the cancer has spread to the surface of the peritoneal cavity. At this stage, it is impossible to surgically remove all apparent lesions, and this accounts for the high rate of cancer recurrence after surgery. Hence, advanced ovarian cancer is the major interest in chemoprevention research. Chemotherapy is the major strategy for the treatment of advanced ovarian cancer, but the disease of this stage usually deteriorates. The cancer cells are prone to gain the capacity of drug resistance against chemotherapeutic agents. Thus, it is very important to further explore the pathogenesis of ovarian cancer, and to find new and effective treatment of ovarian cancer for diagnosis and prevention after operation. MicroRNAs (miRNAs) are evolutionarily conserved, endogenous, small, noncoding, RNA molecules of about 22 nuleotides in length that function as post-transcriptional gene regulators. miRNAs inhibit the expression of target genes by affecting the translation or stability of target mRNA by binding to a target site in the 3′-UTR of target mRNAs. It is revealed that miRNAs regulate various physiological and pathological pathways such as cell differentiation, cell proliferation and tumoriogenesis. miRNAs may function as oncogenes or tumor suppressors, and they involved in many cell signal pathways of tumor formation. Some researcher analyzed miRNAs expression in ovarian tumors and normal ovarian tissues by hybridization of the array. They found some miRNA and miR-100 are down-regulated in ovarian tumors, but the mechanism of miRNAs in ovarian cancer is still not very clear. We analyzed miR-100 expression in 9 serous ovarian cancer tissues and 4 normal ovarian tissues by RT-PCR and proved miR-100 was down-regulated in tumors. In ovarian cancer cell lines, overexpressing miR-100 can reduce ovarian cancer cells resistant to cisplatin and inhibit ovarian cancer tumor angiogenesis in vivo, but do not change the growth of ovarian cancer. We showed miR-100 directly targeting mTOR-3′UTR and inhibited mTOR expression by luciferase assay. So we speculate that miR-100 maybe plays an important role in the ovarian cancer tumorigenesis and angiogenesis through inhibition of mTOR translation. We will further clarify the mechanisms of miR-100 in the ovarian cancer tumorigenesis and angiogenesis and build the network of signaling pathways. Our work may shed light in new strategies for ovarian tumor therapy in future.