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中国癌症防治杂志

中国癌症防治杂志 ›› 2025, Vol. 17 ›› Issue (2): 172-180.doi: 10.3969/j.issn.1674-5671.2025.02.06

• 论著 • 上一篇    下一篇

FAM50A基因敲低介导Caspase 3/PARP凋亡信号通路抑制结直肠癌细胞恶性生物学行为

  

  1. 广西医科大学第一附属医院检验科；广西医科大学基因组与个体化医学研究中心；广西医科大学第一附属医院肝胆外科；广西医科大学附属肿瘤医院肝胆胰腺外科
  • 出版日期:2025-04-25 发布日期:2025-05-15
  • 通讯作者: 宋汉君 E-mail：songhanjun1973@163.comm
  • 基金资助:
    国家科技部高端外国专家引进计划（G2022011018L）；江苏医药职业学院横向课题（A010109）

FAM50A  gene  knockdown suppresses malignant biological behaviors of colorectal cancer cells via the Caspase-3/PARP-mediated apoptotic signaling

  • Online:2025-04-25 Published:2025-05-15

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摘要： 目的 探讨50序列相似的家庭成员A（family with sequence similarity 50 member A, FAM50A）对结直肠癌（colorectal cancer, CRC）细胞增殖、迁移和凋亡的影响及其分子调控机制。方法 通过TCGA和GTEx数据库分析FAM50A在泛癌及CRC中的表达特征及临床意义。采用Western blot检测5对CRC及其癌旁正常组织标本以及5种CRC细胞系（LOVO、RKO、HCT116、SK⁃CO⁃1和SNU175）的FAM50A蛋白表达情况。构建FAM50A稳定敲低的HCT116和RKO细胞株，通过CCK⁃8、Transwell、划痕实验及裸鼠移植瘤模型检测其对细胞增殖、迁移和体内成瘤能力的影响。采用流式细胞术检测细胞凋亡和周期分布。Western blot检测凋亡相关蛋白的表达变化。结果 生物信息学分析显示，FAM50A在肺腺癌、结肠腺癌等16种癌症中均高表达（均P<0.05）；CRC组织中FAM50A mRNA表达水平较正常组织升高（P<0.001），且高表达患者预后更差；结直肠腺癌患者的FAM50A表达高于黏液腺癌患者（P<0.001）。临床样本分析也显示CRC组织中FAM50A蛋白表达水平高于癌旁正常组织（P<0.001）。功能实验结果显示，敲低FAM50A可抑制HCT116和RKO细胞增殖、迁移和裸鼠移植瘤生长（均P<0.01），同时诱导细胞凋亡（均P<0.001）。Western blot结果显示，敲低FAM50A显著上调c⁃Caspase 3、c⁃Caspase 8、c⁃Caspase 9和c⁃PARP蛋白表达水平（均P<0.05）。结论 FAM50A在CRC中高表达且与患者预后不良相关，靶向敲低FAM50A通过激活Caspase 3/PARP凋亡信号通路，抑制CRC细胞增殖和迁移。FAM50A可能是CRC的潜在治疗靶点。

关键词: 结直肠癌, FAM50A, 细胞增殖, 细胞迁移, 细胞凋亡

Abstract: Objective To investigate the effects of family with sequence similarity 50 member A (FAM50A) on the proliferation, migration, and apoptosis of colorectal cancer (CRC) cells and explore its molecular regulatory mechanisms. Methods The expression characteristics and clinical relevance of FAM50A in pan⁃cancer and CRC were analyzed through using TCGA and GTEx databases. The expression of FAM50A protein in 5 pairs of  CRC tissues and adjacent normal tissues were performed by Western blot, as well as in five CRC cell lines (LOVO, RKO, HCT116, SK⁃CO⁃1, SNU175). Stable FAM50A⁃knockdown HCT116 and RKO cell lines were established. The effects on cellular proliferation, migration, and tumorigenesis ability in vivo were assessed through CCK⁃8 assays, Transwell assays, wound healing experiments, and a nude mouse xenograft model. Apoptosis rates and cell cycle were detected via flow cytometry, while the changes in apoptosis⁃related protein expression detected by Western blot. Results Bioinformatics analysis indicated that FAM50A was highly expressed in 16 cancer types, including lung adenocarcinoma and colon adenocarcinoma (all P<0.05). FAM50A mRNA expression levels were significantly higher in CRC tissues than in normal tissues (P<0.001), with high expression correlated with poorer prognosis. FAM50A expression was markedly increased in colorectal adenocarcinoma patients compared with mucinous adenocarcinoma patients (P<0.001). Clinical sample analysis also showed that FAM50A protein expression levels were significantly higher in CRC tissues than in adjacent normal tissues (P<0.001). Functional experiments revealed that FAM50A knockdown suppressed proliferation, migration, and xenograft tumor growth in HCT116 and RKO cells (all P<0.01) and significantly induced apoptosis (all P<0.001). The Western blot results showed that FAM50A knockdown significantly up⁃regulated the expression levels of c⁃Caspase 3, c⁃Caspase 8, c⁃Caspase 9, and c⁃PARP (all P<0.05). Conclusions FAM50A is overexpressed in CRC and associated with poor prognosis. Targeted FAM50A knockdown inhibits CRC cell proliferation and migration by activating the Caspase 3/PARP apoptotic pathway, suggesting its  potential as a therapeutic target for CRC.

Key words: Colorectal cancer, FAM50A, Proliferation, Migration, Apoptosis

中图分类号: 

  • R735.3