Department of Clinical Laboratory, Fujian Medical University Union Hospital, Fuzhou, China.
Department of Clinical Laboratory, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynaecology and Paediatrics, Fujian Medical University, Fuzhou, China.
Gene. 2024 Jul 1;914:148406. doi: 10.1016/j.gene.2024.148406. Epub 2024 Mar 22.
To investigate the mechanism by which S100 calcium-binding protein A6 (S100A6) affects colorectal cancer (CRC) cells to oxaliplatin (L-OHP) chemotherapy, and to explore new strategies for CRC treatment.
S100A6 expression was assessed in both parental and L-OHP-resistant CRC cells using western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), and enzyme-linked immunosorbent assays (ELISA). Lentiviral vectors were utilized to induce the knockdown of S100A6 expression, followed by comprehensive evaluations of cell proliferation, apoptosis, and epithelial-mesenchymal transition (EMT). Additionally, RNA-seq analysis was conducted to identify genes associated with the knockdown of S100A6.
Elevated S100A6 expression in CRC tissues correlated with an adverse prognosis in patients with CRC. Higher expression of S100A6 was also observed in L-OHP-resistant CRC cells, which showed enhanced proliferation, migration, invasion, and antiapoptotic capabilities. Notably, the knockdown of S100A6 expression resulted in decreased proliferation, increased apoptosis, and suppression of EMT and tumorigenicity in L-OHP-resistant CRC cells. Transcriptome sequencing reveals a noteworthy association between S100A6 and vimentin expression. Application of the EMT agonist, transforming growth factor β (TGF-β), induces EMT in CRC cells. S100A6 expression positively correlates with TGF-β expression. TGF-β facilitated the expression of EMT-related molecules and reduced the chemosensitivity of L-OHP in S100A6-knockdown cells.
In conclusion, the knockdown of S100A6 may overcome the L-OHP resistance of CRC cells by modulating EMT.
研究 S100 钙结合蛋白 A6（S100A6）影响结直肠癌细胞对奥沙利铂（L-OHP）化疗的作用机制，并探索结直肠癌治疗的新策略。
使用 Western blot、定量实时聚合酶链反应（qRT-PCR）和酶联免疫吸附试验（ELISA）评估亲本和 L-OHP 耐药结直肠癌细胞中 S100A6 的表达。利用慢病毒载体诱导 S100A6 表达下调，然后全面评估细胞增殖、凋亡和上皮-间充质转化（EMT）。此外，进行 RNA-seq 分析以鉴定与 S100A6 敲低相关的基因。
CRC 组织中 S100A6 的高表达与 CRC 患者的不良预后相关。在 L-OHP 耐药结直肠癌细胞中也观察到 S100A6 的高表达，这些细胞表现出增强的增殖、迁移、侵袭和抗凋亡能力。值得注意的是，S100A6 表达下调导致 L-OHP 耐药结直肠癌细胞增殖减少、凋亡增加，并抑制 EMT 和肿瘤发生。转录组测序揭示了 S100A6 与波形蛋白表达之间的显著关联。EMT 激动剂转化生长因子β（TGF-β）的应用诱导 CRC 细胞发生 EMT。S100A6 表达与 TGF-β 表达呈正相关。TGF-β 促进 EMT 相关分子的表达，并降低 S100A6 敲低细胞中 L-OHP 的化疗敏感性。
总之，S100A6 的敲低可能通过调节 EMT 来克服 CRC 细胞对 L-OHP 的耐药性。
