酪酸梭菌通过调节长链非编码RNAs的表达变化促进结肠癌细胞SW480的凋亡

Clostridium butyricum promotes apoptosis in colon cancer cell line SW480 by dysregulating long non-coding RNAs

目的人结肠癌细胞SW480与酪酸梭菌(Clostridium butyricum,CB)共培养后,检测SW480细胞lncRNAs和mRNAs的应答变化及诱导凋亡的机制。方法 1.5×107CFU/m L酪酸梭菌处理结肠癌细胞48 h后,提取总RNA,对其逆转录RNA并作荧光标记,与安捷伦人lncRNAs/mRNAs芯片杂交。生物信息学预测表达差异的lncRNAs靶基因,并利用DAVID6.7对其进行信号通路富集度分析。双苯并咪唑Hoechst 33258(bisbenzimlde)和Annexin V-FITC/PI染色检测细胞凋亡。结果与SW480对照组相比,共培养酪酸梭菌的结肠癌细胞SW480中的lncRNAs有50个表达上调和152个表达下调的基因,mRNAs中有738个表达上调和1 088个表达下调的基因。对差异表达的基因进行信号通路富集度分析,显示参与肿瘤相关的信号传导途径有MAPK信号通路、细胞因子-细胞因子、JAK-STAT信号、NF-κB的激活、VEGF信号通路和p53信号通路。酪酸梭菌能显著促进结肠癌细胞凋亡。结论酪酸梭菌通过调节lncRNAs的表达变化促进结肠癌细胞SW480凋亡。

Objective To systematically investigate the dysregulation of long non-coding RNAs （lncRNAs） and mRNAs profiles and mechanism for apoptosis induction after co-culture of SW480 cells with Clostridium butyricum （CB）. Methods After SW480 cells were co-cultured with 1.5×10^7CFU/mL CB for 48 h, the total RNA of the cells were extracted and analyzed by Agilent lncRNAs microarray. The SW480 cells without CB treatment served as control. The target genes of dysregulated lncRNAs and dysregulated mRNAs were analyzed by DAVID 6.7 software. Hoechst 33258 （bisbenzimlde） and Annexin V-FITC/PI were used to detect the apoptosis in SW480 cells. Results Compared with the control cells, there were 50 up-regulated lncRNAs and 152 down-regulated lncRNAs, while 738 up-regulated mRNAs and 1 088 down-regulated mRNAs found in the CB-treated cells. After pathway enrichment analysis, these lncRNAs and mRNAs were related to tumor associated signaling pathways, including MAPK signaling, cytokine-cytokine, Jak-STAT signaling, NF-κB activation, VEGF signaling and p53 signaling. Conclusion CB promotes the apoptosis in SW480 cells by dysregulating long non-coding RNAs.