Background. The treatment of cervical cancer in the late stage is still quite challenging, because of nonspecificity in conventional therapies and the lack of molecular targeted drugs. It is necessary to find novel biomarkers for cervical cancer treatment. Methods. In the present study, cervical cell lines HeLa and SiHa with kin17 knockdown were constructed by transfection of the recombinant lentiviral vector carrying KIN17 siRNA and screened by puromycin. The established cells with kin17 knockdown were determined by fluorescence observation and western blotting. Cell apoptosis and the mitochondrial membrane potential (MMP) were detected by flow cytometry. The activity of caspase 3 enzyme was tested by spectrophotometry. The expression profile of apoptosis-associated proteins was analyzed by western blotting. Finally, we used bioinformatics and proteomic data to analyze KIN-related genes in cervical cancer. Results. The results showed high fluorescent positive rates (>90%) and high gene silencing efficiency (>65%) in HeLa and SiHa cells transfected with gene silencing vectors. Moreover, kin17 deficiency decreased the MMP and increased the apoptosis rates in HeLa and SiHa cells, respectively. Furthermore, knockdown of kin17 enhanced the activity of caspase 3 enzyme, increased the expression of cleaved PARP and Bim, while decreasing the expression of Bcl-xL and phosphorylated BAD in HeLa and SiHa cells. Identification of KIN-related prognostic genes in cervical cancer revealed that a total of 5 genes (FZR1, IMPDH1, GPKOW, XPA, and DDX39A) were constructed for this risk score, and the results showed that CTLA4 expressions were negatively correlated with the risk score. Conclusion. Our findings demonstrated that kin17 knockdown facilitates apoptosis of cervical cancer cells by targeting caspase 3, PARP, and Bcl-2 family proteins. Besides, kin17 could regulate cancer cell apoptosis through the mitochondrial pathway and could be used as a novel therapeutic target for the regulation of cell apoptosis in cervical cancer.
基金：
Social Welfare Project of Science and Technology in Zhongshan City of Guangdong Province [2019B1092]; Medical Science and Technology Research Project of Guangdong Province [B2021180]; Start-up Fund for High-level Talents in Affiliated Hospital of Guangdong Medical University [51301Z20200007]; Discipline Construction Project of Guangdong Medical University [4SG21266P, 4SG21276P]
第一作者机构：[1]Zhongshan Torch Dev Zone Peoples Hosp, Zhongshan 528437, Guangdong, Peoples R China[2]Guangdong Med Univ, Dept Med Lab, Affiliated Hosp, Zhanjiang 524000, Guangdong, Peoples R China
通讯作者：
推荐引用方式(GB/T 7714)：
Su Bingsen,Zhong Meifeng,Zhang Yuzhao,et al.Deficiency of kin17 Facilitates Apoptosis of Cervical Cancer Cells by Modulating Caspase 3, PARP, and Bcl-2 Family Proteins[J].JOURNAL OF ONCOLOGY.2022,2022:doi:10.1155/2022/3156968.
APA：
Su, Bingsen,Zhong, Meifeng,Zhang, Yuzhao,Wu, Kunhe,Huang, Qiyuan...&Zeng, Tao.(2022).Deficiency of kin17 Facilitates Apoptosis of Cervical Cancer Cells by Modulating Caspase 3, PARP, and Bcl-2 Family Proteins.JOURNAL OF ONCOLOGY,2022,
MLA：
Su, Bingsen,et al."Deficiency of kin17 Facilitates Apoptosis of Cervical Cancer Cells by Modulating Caspase 3, PARP, and Bcl-2 Family Proteins".JOURNAL OF ONCOLOGY 2022.(2022)
