| 黄 豪,周俊邑,庄 燕,等.SEL1L3 通过对P53信号通路的影响促进结直肠癌细胞增殖[J].肿瘤学杂志,2022,28(8):672-678. |
| SEL1L3 通过对P53信号通路的影响促进结直肠癌细胞增殖 |
| SEL1L3 Enhances Proliferation of Colorectal Cancer Cells through P53 Signal Pathway |
| 投稿时间：2021-11-29 |
| DOI：10.11735/j.issn.1671-170X.2022.08.B008 |
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| 中文关键词: SEL1L3 结直肠癌 P53 凋亡 |
| 英文关键词:SEL1L3 colorectal cancer P53 apoptosis |
| 基金项目:江苏省研究生科研与实践创新计划项目（SJCX21-1154） |
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| 中文摘要: |
| 摘 要：［目的］ 探讨SEL1L3对结直肠癌细胞增殖的影响及其分子机制。［方法］ 分析TCGA数据库中结直肠癌样本SEL1L3表达水平，免疫组织化学染色检测结肠癌组织中SEL1L3的表达水平，Western blot及qPCR检测结肠上皮细胞及结肠癌细胞中SEL1L3表达水平。携带GFP的SEL1L3特异性敲除慢病毒感染RKO细胞，Western blot及qPCR验证SEL1L3敲除效率；荧光显微镜、MTT及平板克隆检测细胞增殖能力，Annexin Ⅴ检测细胞凋亡；细胞凋亡信号通路芯片检测SEL1L3敲除后相关基因的表达，并通过Western blot进行验证。CDX模型检测SEL1L3敲除后RKO细胞在裸鼠体内成瘤能力。［结果］ TCGA数据库分析结果显示SEL1L3在结直肠癌中表达显著高于正常组织。免疫组织化学染色结果表明，SEL1L3在结肠组织中表达显著高于正常组织（6.580±1.103 vs 1.390±0.263，P<0.01），结肠癌细胞中SEL1L3的表达也显著高于正常结肠上皮细胞；细胞增殖实验结果表明，SEL1L3敲除后，细胞增殖能力显著降低（P<0.01）。Annexin Ⅴ检测结果显示，SEL1L3敲除后细胞凋亡明显增多（8.54%±0.41% vs 4.55%±0.27%，P<0.01）。裸鼠CDX模型结果则表明，SEL1L3能够促进RKO细胞在裸鼠体内的生长［（0.98±0.34） g vs（0.30±0.18） g，P<0.01］。细胞凋亡信号通路芯片及Western blot结果显示，SEL1L3表达敲除后，Caspase3（0.450±0.079 vs 1.160±0.115，P<0.01）及P53（0.290±0.018 vs 0.820±0.065，P<0.01）表达显著上调，而XIAP表达则显著下调（1.170±0.071 vs 0.330±0.034，P<0.01）。［结论］ SEL1L3通过上调XIAP表达和抑制P53及Caspase3信号通路，从而促进了结直肠癌的增殖。 |
| 英文摘要: |
| Abstract： ［Objective］ To investigate the effect of SEL1L3 on the proliferation of colorectal cancer cells and its molecular mechanism. ［Methods］ The expression level of SEL1L3 in colorectal cancer samples were collected from TCGA database. Immunohistochemical staining was used to detect the expression level of SEL1L3 in colon cancer tissues. The expression level of SEL1L3 in colon epithelial cells and colon cancer cells was detected by Western blot and qPCR. Human colon cancer RKO cells were infected with SEL1L3 specific knockout lentivirus carrying GFP， the knockout efficiency of SEL1L3 was verified by Western blot and qPCR. Cell proliferation was detected by fluorescence microscopy， MTT， plate cloning and cell spheroidization assay； cell apoptosis was detected with Annexin Ⅴ. The apoptosis signal pathway chip was used to detect the expression of related genes after SEL1L3 knockdown， and it was verified by Western blot. The CDX model was used to detect the tumorigenesis ability of RKO cells in nude mice after SEL1L3 knockout. ［Results］ TCGA database analysis showed that the expression of SEL1L3 in colorectal cancer was significantly higher than that in normal tissues. Immunohistochemical staining showed that the expression of SEL1L3 in colon tissue was significantly higher than that in normal tissue(6.580±1.103 vs 1.390±0.263， P<0.01). The expression of SEL1L3 in colon cancer cell lines was also significantly higher than that in normal colon epithelial cells. The proliferation ability of RKO cells was significantly reduced（P<0.01）， and cell apoptosis increased significantly after EL1L3 knockout(8.54%±0.41% vs 4.55%±0.27%， P<0.01). The results of the nude mouse CDX model showed that SEL1L3 promoted the growth of RKO cells in nude mice ［(0.98±0.34) g vs (0.30±0.18) g， P<0.01］. Apoptosis signal pathway chip showed that after knockout of SEL1L3， the expression of Caspase3(0.450±0.079 vs 1.160±0.115， P<0.01) and P53(0.29±0.018 vs 0.82±0.065， P<0.01) were significantly up-regulated， while the expression of XIAP was significantly down-regulated(1.17±0.071 vs 0.33±0.034， P<0.01). ［Conclusion］ SEL1L3 promotes the proliferation of colorectal cancer by up-regulating the expression of XIAP and inhibiting the P53 and Caspase3 signaling pathways. |
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