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Effect And Mechanism Of ASF1B On Proliferation And Migration Of Cervical Cancer Cells

Posted on:2019-10-20Degree:MasterType:Thesis
Country:ChinaCandidate:J W SongFull Text:PDF
GTID:2504305453473784Subject:Pathogen Biology
Abstract/Summary:PDF Full Text Request
Cervical cancer is the second most common type of female malignancy,subsequent to breast cancer,80% of which are in developing countries.The incidence and mortality of cervical cancer in China account for 1/3 of the global incidence and mortality(1).High-risk HPV persistent infection is a major risk factor for cervical cancer,and more than 90% of cervical cancers are associated with high-risk HPV infection.Although cervical cytology screeninghas enabled early detection and early treatment of cervicalcancer,the incidence and mortality rates continue to increaseeach year(2,3).The majority of patients with cervical cancerare treated with standard radiation therapy and chemotherapy,but therapeutic response varies.Thus,studies are requiredto determine the pathogenesis of cervical cancer in order toidentify a more effective treatment for cervical cancer.In this study,we established anti-silencing functional protein(ASF1B)as a therapeutic target for cervicalcancer treatment.Expression of ASF1 B was higher in cervicalcancer tissues demonstrated by western blot andimmunohistochemistry.Then,the role of ASF1 B in migration and proliferation of cervical cancer cells was investigatedby conducting wound-healing,trans-well assay,cell counting kit(CCK)-8,flow cytometry assay and colonyformation analysis.The data showed that interfering ASF1 B may inhibit the migration and proliferation ofcervical cancer cells by reducing expression of cyclin A,cyclin B1,cyclin D1,Vimentin,and N-cadherin,and by increasing expression of E-cadherin.Additionally,interfering ASF1 B may induce apoptosis of cervical cancer cells byupregulating caspase-3 expression.Furthermore,we use immunoprecipitation method(IP)and liquid chromatography,mass spectrometry(LC-MS)to screen out the interacting protein group with ASF1 B.Then we found that ASF1 B and replication fork protein F1(FOXF1)has a direct interaction by co-immunoprecipitation(CO-IP).In an in vivo model,downregulation of ASF1 B suppressed tumor growthand tumor lung metastasis.In conclusion,ASF1 B is closely associated with migration,proliferation,and apoptosis of cervical cancer cells,and might be considered as a noveltherapeutic target and prognostic indicator in patients with cervical cancer.
Keywords/Search Tags:ASF1B, cervical cancer, proliferation, migration, FOXF1
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