Transcription Factors Gli2 Promotes To Invasion And Metastasis Of Ovarian Cancer Through Regulation MMP7 Expression

Background and Purpose:Ovarian cancer is a frequent malignant tumor in female genitalia,which pathogen is not understand and easy to metastasis and recurrence,which lead to the mortality of ovarian cancer is the first place in female malignant tumor,the 5-year survival rate less than 30% that resulting in a serious threat to the women’s health and life.Exploring the molecular mechanisms of invasion and metastasis of ovarian cancer and proposing treatment measures for targeted therapy will be effective improving the prognosis of patients.Hedgehog(HH)signaling pathway has become a important targets of research field about malignant tumor,the activation of the signaling pathway can be lead to the occurrence and development of a variety of malignancy,including ovarian cancer.So,deep digging the molecular mechanisms of invasion and metastasis of hedgehog signaling pathway in ovarian cancer can provide theory basis for early diagnosis and targeting treatment,and improving survival.Our group had found that MMP7 may be a downstream target gene of Hedgehog signaling pathway and Hedgehog signaling pathway could affect invasion and metastasis of ovarian cancer through the end of transcription factor GLI2 controlling MMP7 expression by microarray analysis,Western Blot,RT-PCR,Transwell invasion assay and Wound Healing experiment in ovarian cancer SKOV3 cells.In order to further exploring Hedgehog signaling pathway influenced invasion and metastasis of ovarian cancer by adjusting MMP7 expression.The research discuss the molecular mechanisms of hedgehog signaling pathways promote invasion and metastasis of ovarian cancer by cellular level,molecular level and organization level,proving the end of transcription factor GLI2(Glioma-associated oncogene2)of hedgehog signaling pathways accelerated invasion and metastasis of ovarian cancer by regulating MMP7(matrix metallopeptidase7)expression,which provides theoretical foundation and scientific basis for ovarian cancer targeted therapy.Research Methods:1.Cultivated SKOV3 cells and compounded CHIP-MMP7 primer,detected whether transcription factors GLI2 of hedgehog signaling pathways interaction with DNA of MMP7 promoter region by Chromatin Immunoprecipitation(CHIP),investigated whether MMP7 interaction with GLI2 facilitating occurrence and development of ovarian cancer.2.Utilized clinical specimens to test the expression quantity of MMP7 and GLI2 of normal ovarian tissue,ovarian benign tumors and ovarian cancer,and whether MMP7 is correlation with GLI2 in ovarian cancer.3.Researched the expression of GLI2 and MMP7 of ovarian cancer are correlation of clinicopathologic factors by analyzing Immunohistochemical results.Results:1.We drew some conclusion by Chromatin Immunoprecipitation(CHIP)assay.The GLI2 group(The PCR template was DNA after GLI2 first antibody processing,the PCR primer was CHIP-MMP7)amplified the sequence that is-8629 to-8457 of MMP7 promoter region,the result showed that transcription factor GLI2 could interaction with the DNA of MMP7 promoter region accelerating MMP7 expression.The Input group as an PCR positive control was normal amplified sequences of MMP7 promoter region;The IgG group as a negative control haven’t amplification products(The PCR template was DNA after IgG first antibody processing,the PCR primer was CHIP-MMP7).2.The expression of GLI2 and MMP7 of ovarian cancer were both more than normal ovarian tissue and benign ovarian tumor,in addition,the expression of GLI2 and MMP7 was a positive correlation by Immunohistochemical experiment.3.We came to some decisions by Immunohistochemical experiment: the expression of GLI2 and MMP7 in advanced ovarian cancer(III/IV stage)are more than in early ovarian carcinoma(I/II stage),the difference is statistically significant(p<0.05);GLI2 and MMP7 expression in lymph node metastases group are higher than in non-lymph node metastases group,the difference is statistically significant(p<0.05);GLI2 and MMP7 expression nothing to do with pathology grade,histological type and have or not ascites,the difference is not statistically significant(p>0.05).Above all indicated that the expression of GLI2 and MMP7 in ovarian cancer tissues are consistent with the relationship of clinicopathologic features,the expression of GLI2 and MMP7 are significantly increased in advanced stage of ovarian cancer(III/IV stage)and couple with lymph node metastases of ovarian cancer tissues.Conclusion:the end of transcription factors GLI2 of hedgehog signaling pathway promotes to invasion and metastasis of ovarian cancer through regulation MMP7 expression.