Anti-Apoptosis Protein TNFAIP8 Affects The Biological Function Of Cervical Cancer Cells

BackgroundCervical cancer is a common female malignant tumor,its global incidence rate is second only to breast cancer.In recent years,the incidence of cervical cancer has become younger,which seriously affects the health and lives of women.In the present prevention and treatment methods,cervical cancer vaccines have appeared on the market that used for early prevention,and surgical treatments such as surgical resection,radiotherapy,and adjuvant chemotherapy have also made tremendous progress.However,many patients have been in the middle and late stages when they were found,and the originally effective treatments have become ineffective.Therefore,there is an urgent need to explore an effective tumor marker for early diagnosis and improvement of treatment strategies.Tumor necrosis factor alpha-inducible protein 8(TNFAIP8 or TIPE)is a recently discovered oncogene and is also referred to as GG2-1,SCC-S2,MDC-3.13.TIPE is highly expressed in a variety of cancers and is involved in the proliferation,migration and invasion of tumor cells,inhibits the apoptosis of tumor cells and reduces the sensitivity of tumor cells to chemotherapeutic drugs.It has been shown in the study that TIPE is highly expressed in endometrial cancer in female tumors,and highly correlated with the expression of MMP-9 and proliferative antigen Ki-67 in the development of endometrial cancer.In ovarian cancer,TIPE has a certain correlation with the clinicopathological features and prognosis of tumors,but the mechanism of TIPE expression and involvement in regulating the growth,invasion,and migration of cervical cells has not yet been determined.Therefore,it is significant to study the effect of TIPE on the proliferation,migration and apoptosis of cervical cancer cells and the exact mechanism,to find and find a new target of intervention for the treatment of cervical cancer and improve the prognosis of patients.ObjectiveTo investigate the effects of TIPE on the proliferation,invasion,metastasis and apoptosis of cervical cancer cells and related mechanisms,so as to provide basis for early clinical diagnosis and targeted therapy of cervical cancer.MethodsThe expression of TIPE in cancer tissues and paracancerous tissues of clinical cases was measured byimmunohistochemical technique,and the expression differences of TIPE in cancer tissues and adjacent tissues were analyzed.The TIPE gene was knocked out in three cervical cancer cells,HeLa,C-33 A,and SiHa.A stable cell line was obtained by puromycin selection.The effects of TIPE on the proliferation of cervical cancer cells were detected by MTS assay.The effects of TIPE on the migration of cervical cancer cells were analyzed by scratch and Transwell assays.The effect of TIPE on the invasion of cervical cancer cells was analyzed by Matrigel assay.The effect of TIPE on the apoptosis of cervical cancer cells was detected by flow cytometry and TUNEL,and the expression of related apoptotic proteins in TNFR1 receptor signaling pathway was detected by Western Blot.A tumor model of nude mice was established to analyze the effect of knocking down TIPE on tumor formation in nude mice.ResultsThe results of immunohistochemistry showed that the expression level of TIPE in paracancerous tissues of the cervix was lower than that of cancer tissues.Knock down the expression of TIPE in HeLa,C-33 A and SiHa cell lines of cervical cancer and reduce the proliferation of cervical cancer cells,The results of MTS showed that the cells was significantly lower than the control cells;The results of the scratch,Transwell and Matrigel experiments combined with the detection level of related invasive proteins MMP2 and MMP9 showed that knocking down TIPE can significantly reduce the migration and invasion of cervical cancer cells HeLa,C-33 A and SiHa;The results of TUNEL and the flow cytometry showed that the cells which were knockouted TIPE,have lower anti-apoptosis ability than the control group cells.In addition,the results of Western Blot showed that the expression of related apoptosis proteins such as FADD,casepase3,casepase9,p-JNK,Bax ect.in the TNFR1 pathway increased;nude mice experiment showed that knocking down of TNFAIP8 reduced the growth rate and tumor formation rate of nude mice.ConclusionTumor necrosis factor-α-induced protein 8(TIPE)promotes the proliferation,invasion and metastasis of cervical cancer cells and inhibits its apoptosis.