The Mechanism Of Stathmin1(STMN1) Promoting Tumor Cell Invasion And Migration And Inducing Chemo-resistance In The Cervical Cancer Cells

【Objective】 Statmin1(STMN1)is a microtubule-destabilizing protein that reorganizes cytoskeleton and regulates cell cycle,differentiation,apoptosis and function.Previous studies have reported high expression of STMN1 in a wide variety of human cancers.Besides,the disorder of STMN1 expression in patients with cervical cancer or cervical intraepithelial neoplasia(CIN)Ⅲ can be used as a marker in clinical prognosis.In this part,we investigated the effect of STMN1 on the progression in cervical cancer cell as well as its mechanism.【Method】 1.Using Oncomine Database analyzed of STMN1 expression in Cervical Squamous Cell Carcinoma and Cervical Squamous Cell.Collecting the cancer tissues and adjacent normal tissues of cervical carcinoma patients diagnosed by postoperative pathological examination.The m RNA expression was conducted by real-time PCR(RT-PCR).The protein expression of studied genes was detected by Western blotting as well as immunohistochemical analysis.2.Small Interfering RNA(si RNA)was used to inhibit the expression of STMN1 in cervical cancer cell Siha and C33 A.Transwell assays were conducted to see whether STMN1 had an effect on cervical cancer cell migration and invasion or not in si-NC group and si-STMN1 group.3.The total RNA derived from the cells as well as the tissues was extracted,after that the m RNA level was quantified though real-time PCR.【Result】 1.STMN1 is frequently overexpressed in cervical cancer tissues.Oncomine data showed that the expression of STMN1 in cervical squamous cell carcinoma was significantly higher than that in cervical squamous epithelium.Both m RNA and protein of STMN1 was significantly highly in cervical cancer tissues compared with that in adjacent normal tissues.2.STMN1 promotes migration and invasion of cervical cancer cells in vitro.The ability of migration and invasive was estimated by Transwell assay.It was found that STMN1 si RNA could weaken the capability of migration and invasion in Siha and C33 A.3.STMN1 regulated the expression of MMP-2 and MMP-9 protein levels.Real time PCR and Western blotting showed that the suppression of STMN1 in cervical cancer resulted reduction in the levels of MMP-2 and MMP-9.【Conclusion】 Compared with normal tissues,STMN1 expression of cervical carcinomas was markedly elevated.Suppression STMN1 by means of transfecting si RNA accelerates migration/invasion in vitro assays,according with low expression of the MMP-2/MMP-9.This switch accelerated cancer cell metastasis.In summary,our study provided evidence linking STMN1 to progression in cervical cancer and elucidated the underlying mechanism.【Objective】 Previous studies have demonstrated that high expression of STMN1 play a pivotal role in human cervical cancer,especially during the progression of this disease.Besides,the disorder of STMN1 expression in patients with malignant tumor can be used as a marker in clinical prognosis because of the strong correlation between the high expression of STMN1 and poor clinical prognosis.In this study,we investigated the effect of STMN1 on the chemo-resistance in cervical cancer cell as well as its mechanism.【Method】 1.Small Interfering RNA(si RNA)was used to inhibit the expression of STMN1 in cervical cancer cell Siha and C33 A.2.The sensitivity of Cervical cancer cell to cisplatin after treatment with STMN1 si RNA was estimated via Cell counting kit.3.Flow cytometry was applied to test cell apoptosis after treatment with STMN1 si RNA or si RNA Negative Control.4.The total RNA derived from the cells as well as the tissues was extracted,after that the m RNA level was quantified though real-time PCR.【Result】 1.CCK8 assay demonstrated that compared with Negative Control,down-regulation of STMN1 could increase the sensitivity of Siha and C33 A to cisplatin.Cisplatin dose-dependently increased the protein level of STMN1.2.Results proved that the combination use of si NC and cisplatin showed not significant effect on the apoptosis,while the combination use of si STMN1 and cisplatin could significantly promote the cisplatin induced apoptosis.3.Moreover,the western blotting results show that the combinational use of si STMN1 and cisplatin could also active the apoptosis pathways.These findings suggested that si STMN1 could sensitize of cervical cancer cells to DDP via inactivation of cisplatin induced anti-apoptosis.【Conclusion】 In summary,our study provided evidence linking STMN1 to progression in cervical cancer and elucidated the underlying mechanism.Down-regulation of STMN1 could sensitize cervical cells to cisplatin via activation of cisplatin induced apoptosis.Notably,it provides a new theoretical basis and therapeutic strategy for improving the sensitivity of cisplatin chemotherapy by targeting STMN1 in cervical cancer.