Functions Of HLTF In Cervical Cancer

Purpose:In recent years,cervical cancer remains one of the most common malignancies in women and the death rate remains high,despite the introduction of the HPV vaccine and the use of multiple screening tools.The basic treatments of cervical cancer are platinum-based chemotherapy and radiotherapy,but the 5-year survival rate of patients with advanced cervical cancer is still poor.Therefore,we explore the role and the related functions of HLTF gene in the occurrence and development of cervical cancer and chemotherapy,providing a new direction for targeted treatment research.Methods:The expression level of HLTF in cervical cancer tissues and adjacent tissues was analyzed by real-time PCR.The different expression levels of HLTF in the normal cervical group,the cervical cancer group without lymph node metastasis,and the cancer group with lympa node metastasis were analyzed by immunohistochemistry.We compared the expression levels of HLTF in four cervical cancer cell lines,including SiHa,HeLa,C-33A and CaSki cells.After knocking down HLTF genes in cervical cancer cell lines,real-time PCR and WB were used to detect the DNA and protein levels of HLTF.The effect of HLTF on cell growth was determined by CCK-8 assay.Changes in cell apoptosis were analyzed by flow cytology,and changes in protein levels in apoptosis-related pathways were analyzed by WB.Meanwhile,immunofluorescence technology was used to detect the changes of ?-H2AX foci in cells after knockdown of HLTF.Results:The expression level of HLTF in cervical cancer tissues was significantly higher than that in adjacent tissues,and its expression levels may be related to the malignant progression of cervical cancer.Knockdown of HLTF inhibited cell proliferation and promoted apoptosis,upregulated the levels of ?-H2AX and cleaved caspase-3 in cells,activated ATR/CHK1 pathway and homologous recombinant repair pathway,and the levels of ?-H2AX foci were increased in the nucleus.Conclusions:HLTF is highly expressed in cervical cancer.Knockdown of HLTF can inhibit its proliferation with promoting apoptosis,and meanwhile affect relevant proteins in ATR/CHK1 pathway and homologous recombination repair pathway.These studies suggest that HLTF may provide new targets for the treatment of cervical cancer in the future.