Study Of Mechanism Of The Effect Of Oct4 On The Proliferation And Invasiveness Of Epithelial Ovarian Cancer Side Population Cells

Ovarian cancer is one of the most common gynecologic malignances in China.Although surgery,chemotherapy,and radiotherapy eliminate clinically apparent ovarian tumor,the 5-year survival rate is no more than 45%.Cancer stem cells(CSCs)have been identified for precaution of tumor metastasis and recurrence in many kinds of cancers including ovarian cancer.Oct4(POU class 5 homeobox 1,POU5F1),a transcription factor has the potential to maintain self-renewal and pluripotency in ESCs and primordial germ cells,is frequently expressed in ovarian cancer at elevated level.However,the specific roles of Oct4 and its underlying molecular mechanism in the progression of ovarian cancer have not yet been completely elucidated.Research purposes: This study aims to explore the function of Oct4,a CSC marker,in ovarian cancer progression and to investigate its underlying mechanism.Through in vitro and in vivo assays,biological functions of Oct4 during ovarian cancer progression were discovered,further elucidating the potential role of the molecular mechanisms of tumor side population cells in regulating tumor cell proliferation,invasion,apoptosis,and metastasis.Research methods: By Hoechst side population(SP)technique,CSC-like SP cells from human ovarian cancer SKOV3 and A2780 cells were isolated and used for this study.sh RNA and lentivirus targeting human Oct4 gene were used to knock down Oct4 in SP cells and upregulate Oct4 in non-SP(NSP)cells stably.Peficitinib was used to inhibit JAK/STAT signaling.Cell counting kit-8,flow cytometry,and in vivo xenograft model were used to evaluate the effects of Oct4/JAK/STAT on the viability,drug resistance,apoptosis,cycle,and tumorigenesis of the SP cells.Immunofluorescence staining was used to detect the location of STAT6.Research results: Results showed that Oct4 was upregulated in the SP of SKOV3 and A2780 cells when compared with the NSP cells.Downregulation of Oct4 inhibited SP cell viability,tumorigenesis,and reduced cell drug resistance and induced a G2/M phase arrest,while upregulation of Oct4 conferred NSP cell malignant features.Besides,Oct4 upregulation in NSP cells increased the phosphorylated levels of proteins in JAK and STAT families,especially in JAK1 and STAT6.Furthermore,the roles of apoptosis inhibition and viability,invasion,and tumorigenesis promotions induced by Oct4 in NSP cells were all abolished when adding peficitinib.Conclusion: In conclusion,our study demonstrated that Oct4 was highly expressed in the SP population of SKOV3 and A2780 ovarian cancer cells.Downregulation of Oct4 distinctly decreased the viability,tumorigenesis,and drug resistance of SP cells,and Oct4 upregulation endowed the NSP of ovarian cancer cells malignant features.Moreover,our study demonstrated that Oct4 accelerated ovarian cancer progression through activating JAK/STAT signaling pathway.Overall,our study suggested that Oct4/JAK/STAT should be served as a potent target for ovarian cancer treatment.