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.

中文翻译：

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S100A6介导的上皮间质转化影响结直肠癌对奥沙利铂的化疗敏感性

探讨S100钙结合蛋白A6（S100A6）影响结直肠癌（CRC）细胞对奥沙利铂（L-OHP）化疗的机制，探索CRC治疗新策略。使用蛋白质印迹、定量实时聚合酶链反应 (qRT-PCR) 和酶联免疫吸附测定 (ELISA) 评估亲代和 L-OHP 耐药 CRC 细胞中的 S100A6 表达。利用慢病毒载体诱导S100A6表达敲低，然后综合评估细胞增殖、凋亡和上皮间质转化（EMT）。此外，还进行了 RNA-seq 分析来鉴定与 S100A6 敲低相关的基因。 CRC 组织中 S100A6 表达升高与 CRC 患者的不良预后相关。在 L-OHP 耐药的 CRC 细胞中也观察到 S100A6 的较高表达，显示出增强的增殖、迁移、侵袭和抗凋亡能力。值得注意的是，S100A6 表达的敲低导致 L-OHP 耐药 CRC 细胞增殖减少、细胞凋亡增加、EMT 和致瘤性受到抑制。转录组测序揭示了 S100A6 和波形蛋白表达之间的显着关联。应用 EMT 激动剂转化生长因子 β (TGF-β) 可诱导 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细胞的L-OHP抵抗。