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线粒体核糖体蛋白S35对结肠癌细胞增殖、侵袭和迁移的调控作用及机制研究

Regulatory role and mechanism of mitochondrial ribosomal protein S35 in proliferation, invasion, and migration of colon cancer cells

    摘要
  • 摘要: 目的 探讨线粒体核糖体蛋白S35(MRPS35)对结肠癌细胞增殖、侵袭和迁移的调控作用及机制。方法 收集120例结肠癌根治术患者的结肠癌组织及癌旁正常组织标本,培养人结肠癌细胞系(HCT116、SW480、SW620)和人正常结肠上皮细胞系(NCM460)。通过生物信息学分析、实时荧光定量聚合酶链反应、蛋白质印迹法(Western blot)、免疫组织化学(IHC)分析、细胞功能实验(平板克隆形成实验、划痕实验、Transwell细胞迁移实验、CCK-8细胞活力实验)等方法评估MRPS35在结肠癌中的表达及调控机制。结果 生物信息学分析结果显示, MRPS35基因在结直肠癌组织中的表达水平高于癌旁正常组织，差异有统计学意义(P<0.05)。人结肠癌细胞系(HCT116、SW480、SW620)中MRPS35 mRNA和MRPS35蛋白相对表达量均高于NCM460细胞，差异有统计学意义(P<0.05); 结肠癌组织中的MRPS35蛋白相对表达量高于癌旁正常组织，差异有统计学意义(P<0.05)。MRPS35表达水平与肿瘤直径、肿瘤分化程度、T分期显著相关(P=0.002、0.021、0.036)。MRPS35高表达患者的总体生存率高于MRPS35低表达患者，差异有统计学意义(Log-rank P=0.015)。敲低MRPS35后，结肠癌细胞克隆、增殖、侵袭、迁移能力均显著增强。敲低MRPS35后, Wnt1、β-Catenin及其下游靶标蛋白的表达显著增加。结论 MRPS35在结肠癌组织和结肠癌细胞中均显著高表达，其可能通过调控Wnt/β-Catenin信号通路抑制结肠癌的发生与发展，有望成为结肠癌的新型生物标志物和潜在治疗靶点。

     

    Abstract: Objective To investigate the regulatory role and mechanism of mitochondrial ribosomal protein S35 (MRPS35) in the proliferation, invasion, and migration of colon cancer cells. Methods A total of 120 colon cancer tissues and adjacent normal tissues from patients undergoing radical resection for colon cancer were collected. Human colon cancer cell lines (HCT116, SW480, SW620) and a human normal colon epithelial cell line (NCM460) were cultured. Bioinformatics analysis, real-time quantitative polymerase chain reaction, Western blot, immunohistochemical (IHC) analysis, and cellular functional experiments (plate clone formation assay, scratch test, Transwell migration assay, CCK-8 cell viability assay) were conducted to evaluate the expression and regulatory mechanism of MRPS35 in colon cancer. Results Bioinformatics analysis showed that the expression level of the MRPS35 gene was higher in colorectal cancer tissues than in adjacent normal tissues (P<0.05). The relative expression levels of MRPS35 mRNA and MRPS35 protein were higher in human colon cancer cell lines (HCT116, SW480, SW620) than in NCM460 cells (P<0.05). The relative expression level of MRPS35 protein was higher in colon cancer tissues than that in adjacent normal tissues (P<0.05). The expression level of MRPS35 was significantly correlated with tumor diameter, tumor differentiation, and T stage (P=0.002, 0.021, 0.036). Patients with high MRPS35 expression had a higher overall survival rate than those with low MRPS35 expression (Log-rank P=0.015). After knockdown of MRPS35, the abilities of colon cancer cell cloning, proliferation, invasion, and migration were significantly enhanced. Furthermore, the expression of Wnt1, β-Catenin, and their downstream target proteins increased significantly after MRPS35 knockdown. Conclusion MRPS35 is significantly overexpressed in both colon cancer tissues and colon cancer cells, and it may inhibit the occurrence and development of colon cancer by regulating the Wnt/β-Catenin signaling pathway. Therefore, MRPS35 has the potential to become a novel biomarker and therapeutic target for colon cancer.

     

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