The Role Of LncRNA SOX2OT Induced Proliferation,Migration And Invasion In Ovarian Cancer

Ovarian cancer is one of the most common malignant gynecological cancers and has the highest overall mortality rate and 5-year survival rate,with a large burden on global public health.Although the surgical resection in combination with the conventional chemotherapies have made some progression in the treatment of ovarian cancer patients.However,the vast majority of patients with advanced disease relapse within 5 years,often caused by the metastasis of ovarian cancer cells.It is very urgent to identify novel molecular targets in tumor diagnosis and therapy for many women affected by this disease.Long non-coding ribonucleic acid(lncRNA)SRY-box 2 overlapping transcript(SOX2OT)is a transcription factor which is essential for the maintenance of self-renewal,the pluripotency of undifferentiated embryonic stem cells and tumorigenesis.LncRNA SOX2OT are involved in multiple key biological processes of human diseases,including cancer,and has currently become one of the focuses of cancer studies.Recent studies suggested that lncRNA function as a crucial component of complex gene regulatory network by regulating gene expression at the transcriptional,post-transcriptional and epigenetic levels,and it may play an important role in cell proliferation,differention and apoptosis,but the concrete mechanism of how lncRNA SOX2OT works on ovarian cancer in the carcinogenesis,development and metastasis remains unclear.Recently,there were a few reports about the correlation between lncRNA SOX2OT and other tumor at home and aboard,however there were no report about the correlation of lncRNA SOX2OT and ovarian cancer.So,there has a very important clinic value to study the expression of IncRNA SOX2OT in ovarian cancer and the mechanism of how lncRNA SOX2OT works on ovarian cancer in the propagation,migration and invasion.This research consists of the following three parts:?the quantitative real-time polymerase chain reaction(q RT-PCR)to detect lncRNA SOX2OT expression in 105 cases of ovarian cancer tissues and normal tissues adjacent to carcinoma and ovarian cancer cell line;analysis of the correlation of the expression and clinicopathological features of ovarian cancer;evaluate lncRNA SOX2OT prognostic significance in patients with ovarian cancer.?The knockdown of SOX2OT by specific small interfering RNA(siRNA)transfection of the ovarian cancer cell,establish lncRNA SOX2OT low-expressed ovarian cancer lines,further studies on lncRNA SOX2OT biological function in ovarian cancer were determined by colony formation assay,cell cycle analysis as well as cell migration and invasion assay.?Using the western-blot method to detect the key cell cycle regulator Cyclin B1,Cdc25C and the markers of epithelial-mesenchymal transitions(EMT)including mesenchymal N-cadherin and epithelial E-cadherin in HO-8910PM cells with siSOX2OT transfection,sequentially to definitude the exact molecular mechanism of lncRNA SOX2OT effect proliferation and invasive of ovarian cancer.Part ? Expression and clinical significance of lncRNA SOX2OT in ovarian cancerObjectives:To investigate the expression of lncRNA SOX2OT and its correlation with clinicopathologic characteristics and prognosis of patients with ovarian cancer.Methods:The expression of lncRNA SOX2OT was detected by quantitative real-time PCR in 105 ovarian cancer specimens and cell lines.Standard statistical analysis was used to evaluate correlation between lncRNA SOX2OT and clinicopathological features and its prognostic significance in ovarian cancer.Results:lncRNA SOX2OT expression was increased in ovarian cancer tissues and cultured ovarian cancer cells compared with adjacent non-tumor tissues(P<0.05).The relative transcript level of SOX2OT was synchronously higher in HO-8910PM cells than that in HO-8910 cells(P<0.05).Statistical analysis revealed that the high expression of SOX2OT was positively correlated with age of onset,tumor size,higher TNM stages,and lymphatic metastasis(P<0.05).However,no significant correlation was observed between the expression of SOX2OT and familial status in ovarian cancer patients(P>0.05).Conclusions:?High lncRNA SOX2OT expression was correlated with the age of onset,tumor size,higher TNM stages,and lymphatic metastasis.However,there was no statistically significant association between the expression of SOX2OT and familial status.?The abnormal expression of lncRNA SOX2OT might be associated with ovarian cancer progression.Part ? Studies on the molecular mechanism of IncRNA SOX2OT in the migration and invasion of ovarian cancer Objectives: Investigate the molecular mechanism of IncRNA SOX2OT in the proliferation,migration and invasion of ovarian cancer Methods: The knockdown of S0X20T by specific siRNA transfection of the ovarian cancer cell,establish IncRNA S0X20T low-expressed ovarian cancer lines,further studies on IncRNA S0X20T biological function irx ovarian cancer were determined by colony formation assay,Cell cycle analysis as well as Cell migration and invasion assay.Results:When HO-8910 PM cells were transfected with siRNA,the relative expression of S0X20T was notably decreased.(2)It was shown that both siRNA could effectively suppress the colony formation capacity of HO-8910 PM cells by up to 50%.cell cycle analysis showed that more than 15% cells were arrested in G0/G1 phase when SOX2OT was knocked down with both siRNA in HO-8910 PM cells;meanwhile,tiie percentage of cells in S and G2/M phases was accordingly decreased.?The transwell migration assays and cell invasion assay suggested that the number of cells migrated through the chamber and adhered to the lower surface of the membrane dropped by transfection of siR-S0X20T-l5 and even dramatically when cells were treated with the second siRNA(siR-S0X20T-2).Conclusions: LncRNA SOX2OT promoted cell proliferation,motility and invasion in ovarian cancer cells and associated with the outcome of ovarian cancer patients,which indicated that SOX2OT might serve as a potential therapeutic target in the treatment of ovarian cancer.Part ? Studies on the mechanism of IncRNA SOX2OT promoted proliferation and metastasis of ovarian cancer via cell-cycle regulation and EMT path Objectives: Investigate the mechanism of IncRNA SOX2OT promoted proliferation and metastasis of ovarian cancer via cell-cycle regulation and EMT path.Methods: Using the western-blot method to detect the key cell cycle regulator Cyclin Bl,Cdc25 C and EMT markers including mesenchymal N-cadherin and epithelial E-cadherin in HO-8910 PM cells with siSOX2OT transfection,sequentially to definitude the exact molecular mechanism of IncRNA SOX2OT promote proliferation and invasive of ovarian cancer.Results: When SOX2OT was knocked down by specific siRNAs,the protein levels of Cyclin Bl,Cdc25 C and N-cadherin were all decreased,whereas the protein level of E-cadherin was increased after knockdown of SOX2OT.Conclusions: S0X20T positively regulates tumor growth in ovarian cancer.? The functions that knockdown of SOX2OT inhibited cell proliferation and motilities in cultured ovarian cancer cells may be achieved by arresting cell cycle and promoting EMT processes.?EMT activation in ovarian cancer is associated with chemoresistance,So EMT program might also work as a potential target for the diagnosis and treatment of ovarian cancer.