Metastatic colorectal cancer (mCRC) patients are treated with standard chemotherapeutic drugs in the form of FOLFOX and FOLFIRI regimens. There are no reliable markers that could predict response to chemotherapy for mCRC. TGF-β signaling which interacts with microRNA (miRNA) network has important roles in tumor progression and chemotherapy resistance, thus the interplay between TGF-β signaling and miRNAs could be crucial for treatment response. The aim of this study was to analyze the effect of chemotherapy for mCRC on TGF-β signaling and related miRNAs. Hsa-miR-17-5p, hsa-miR-21-5p and hsa-miR-93-5p were selected out of 316 miRNAs with multiple targets within the TGF‐β signaling by in silico analysis. SW620 cells were treated with chemotherapeutic drugs for mCRC for 1, 3 and 6 days and expression of selected miRNAs, PAI-1, CDH1 and VIM was measured. Expression of TGF‐β signaling-related hsa-miR-17-5p, hsa-miR-21-5p and hsa-miR-93-5p was time-dependently altered in SW620 cells treated with chemotherapeutics for mCRC. The expression of hsa-miR-93-5p remained downregulated after 6 days under combined treatments FOX and FIRI as well as the hsa-miR-17-5p expression under FIRI. Chemotherapy regimens for mCRC increased expression of a major TGF‐β signaling target gene PAI-1, independently of the selected miRNAs expression. These treatments also increased the expression of epithelial-mesenchymal transition (EMT) markers CDH1 and VIM on day 3 resulting in decrease of mesenchymal-like characteristics. However, their expression returned close to basal level on day 6. In conclusion, after initial response to chemotherapeutic drugs SW620 cells start to return close to the basal mesenchymal state while the long-term downregulated expression pattern of hsa-miR-93-5p and hsa-miR-17-5p makes them candidates worth testing as biomarkers for monitoring combined chemotherapeutic treatments therapy response in mCRC patients.

转移性结直肠癌 (mCRC) 患者接受 FOLFOX 和 FOLFIRI 方案形式的标准化疗药物治疗。没有可靠的标记物可以预测转移性结直肠癌化疗的反应。与 microRNA (miRNA) 网络相互作用的 TGF-β 信号传导在肿瘤进展和化疗耐药中发挥重要作用，因此 TGF-β 信号传导与 miRNA 之间的相互作用对于治疗反应可能至关重要。本研究的目的是分析 mCRC 化疗对 TGF-β 信号及相关 miRNA 的影响。通过计算机分析，从 316 个具有 TGF-β 信号传导多个靶标的 miRNA 中选出 hsa-miR-17-5p、hsa-miR-21-5p 和 hsa-miR-93-5p。用mCRC化疗药物处理SW620细胞1、3和6天，并测量所选miRNA、 PAI-1 、 CDH1和VIM的表达。在接受 mCRC 化疗药物治疗的 SW620 细胞中，TGF-β 信号传导相关的 hsa-miR-17-5p、hsa-miR-21-5p 和 hsa-miR-93-5p 的表达呈时间依赖性变化。在FOX和FIRI联合处理下6天后，hsa-miR-93-5p的表达以及FIRI下hsa-miR-17-5p的表达仍然下调。 mCRC 的化疗方案增加了主要 TGF-β 信号传导靶基因PAI-1的表达，与所选 miRNA 的表达无关。这些治疗还增加了第 3 天上皮-间质转化 (EMT) 标记物CDH1和VIM的表达，导致间质样特征减少。然而，他们的表达在第 6 天恢复到接近基础水平。 总之，在对化疗药物产生初步反应后，SW620 细胞开始恢复接近基础间充质状态，而 hsa-miR-93-5p 和 hsa-miR-17-5p 的长期下调表达模式使它们成为值得测试的候选者用于监测 mCRC 患者联合化疗治疗反应的生物标志物。