| OBJECTIV:Ovarian cancer(OC)is a fatal malignancy in women worldwide,and its poor prognosis is mainly due to metastasis.Ovarian cancer is only associated with vague and mild symptoms in the early stages of disease onset and progression(FIGO stage I-II),which greatly hindering early detection and diagnosis.Therefore,approximately 75%of patients with ovarian cancer are diagnosed with ovarian cancer when the tumor has spread extensively to the peritoneal cavity(FIGO stage III-IV).High grade serous ovarian cancer(HGSOC)is the main histological subtype of ovarian cancer,accounting for more than 70%.It is also the type with the lowest survival rate and the highest mortality.The 5-year Overall survival(OS)was less than 40%.At present,tumor cytoreductive surgery and platinum-based adjuvant chemotherapy are still the preferred treatment for HGSOC.Although most patients achieve clinical remission after ideal resection and satisfactory chemotherapy treatment,70%of them will still relapse,which is attributed to the common chemotherapeutic resistance of HGSOC.The patient eventually died due to the lack of effective treatment,and the median progression-free survival(PFS)was only 18 months.In recent years,microRNA(miRNA/miR)has been found to play an important role in the development of a variety of tumors by affecting the expression of their targets.MiRNA(microRNA)is a kind of single-stranded RNA with a length of about 22 nucleotides.It has been found and studied in both plants and animals,and accounts for about 3%of the total genome in humans.The biological functions of miRNA have been revealed by a large number of studies.MiRNA participates in the regulation of biological processes such as cell proliferation,apoptosis and metastasis by regulating the expression of tumor suppressor genes or oncogenes,and thus plays an essential role in the occurrence and development of cancer.A large number of literatures have reported that Mir-10b,Mir-125b and Mir-145 are inhibited in the process of tumorigenesis,while Mir-21 and Mir-155 are upregulated in the process of tumorigenesis,respectively acting as tumor suppressor genes or oncogenes.However,the biological role and potential mechanism of Mir-489 in OC need to be further elucidated.MATERIALS AND METHODS:Quantitative Real-Time-Polymerase Chain Reaction(qRT-PCR)was utilized to confirm the miR-489 expressions in OC tissue samples and cell lines.The functions of miR-489 were analyzed by performing functional assays,such as MTT assays and transwell assays.The effect of miR-489 on platinum sensitivity of high-grade ovarian serous carcinoma was demonstrated by the cell activity experiments of cisplatin gradient treatment of miR-489 overexpressed SKOV3 and miR-489 downexpressed OVCAR3 and the tumor formation experiment of nude mice.The downstream target of miR-489 was confirmed by TargetScan and lucifer-ase reporter assay.Western blot was conducted to detect the expression of indicators associated with the down-stream signaling pathway.RESULTS:MiR-489 was prominently down-regulated in OC tissues and cells,and the decreased miR-489 expression was related to malignant clinicopathologic features and poor prognosis of OC patients.Functional assays demonstrated that miR-489 could suppress OC cell viability,invasion,and migration.X-linked inhibitor of apoptosis protein(XIAP)was iden-tified as a target of miR-489 and partially regu-lated the functions of miR-489 in OC.Moreover,we found that miR-489 inhibits OC progression via regulating phosphatidyl-inositol3-kinase/protein-kinase-B pathway(PI3K/AKT)and epithelial-to-mesenchymal transition(EMT).CONCLUSION:Our results indicate that Mir-489 inhibits the development of ovarian cancer,exerts anti-ovarian cancer effects by directly acting on XIAP and regulating PI3K/AKT and epithelial-mesenchymal transition signaling pathways,and may be used as a therapeutic target for ovarian cancer.Further studies on the potential applications and implications of miR489 are ongoing. |
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