卡介苗接种是临床上治疗癌症的一种方法。但近期研究人员却发现，卡介苗感染肿瘤细胞后，能使细胞对肿瘤坏死因子-α(TNF-α)诱导的凋亡作用产生抗性。而参与这一过程的细菌组分及其作用机制还有待研究。本项目前期实验结果显示卡介苗的外分泌蛋白MPB83与宫颈癌细胞共孵育后，可以通过增强NF-κBp65核转位抑制PTEN蛋白表达，进而抑制TNF-α诱导的细胞凋亡。同时前期生物信息学预测结果显示，miR-130b基因表达不仅可以介导NF-κBp65核转位对PTEN蛋白表达的抑制作用，而且还能反馈调控NF-κBp65核转位。本项目拟用荧光素酶报告基因检测系统等实验手段证实信息学的预测结果，并以此揭示miR-130b基因表达介导NF-κBp65核转位抑制PTEN蛋白表达以及调控NF-κBp65核转位的机制，解释MPB83蛋白抑制宫颈癌细胞凋亡的现象，最终为临床上应用卡介苗治疗肿瘤存在风险的推测提供依据。

Intravesical Bacille Calmette-Guerin (BCG) therapy has been proved to be a useful way in treating cancer in clinic. However, recent research showed that tumor cells infected by BCG exhibit resistant to apoptosis induced by TNF-αreagent, but which bacterial component is involved and how it works in this procedure are still unknown. The data acquired from our previous research showed that the incubation of cervical cancer cells with the MPB83 protein, a secreted protein derived from Bacille Calmette-Guerin, could decrease the apoptosis ratio of tumor cells induced by TNF-α relying on suppressed expression of PTEN protein which was caused by the enhancement of NF-κBp65 nuclear translocation. On the basis of bioinformatics analysis, we considered that miR-130b not only participated in the down-regulation of PTEN protein expression caused by the enhanced NF-κBp65 nuclear translocation but also resulted in the enhancement of NF-κBp65 nuclear translocation. Our study aims to confirm the conclusion reached according to the bioinformatics data analysis using the experimental methods such as luciferase reporter assays. And then we can reveal the mechanisms by which the miR-130b mediated the down-regulated expression of PTEN protein caused by the enhanced NF-κBp65 nuclear translocation and by which the increased expression of miR-130b gene enhanced the NF-κBp65 nuclear translocation based on the experimental data. The uncovered mechanism will be beneficial to understand how the MPB83 protein inhibits the apoptosis of tumor cells and to offer an evidence to support the hypothesis that there may be a potential danger in treating cancer using BCG therapy in clinic.