PDF(Pubmed)
Abstract：
Introduction: One of the primary obstacles faced by individuals with advanced colorectal cancer (CRC) is the potential development of acquired chemoresistance as the disease advances. Studies have indicated a direct association between elevated levels of miR-92a-3p and the progression, metastasis, and chemoresistance observed in CRC. We proposed that miR-92a-3p impairs FOLFOX (fluorouracil/oxaliplatin) chemotherapy response by upregulating the expression of chemoresistance biomarker genes through the activation of β-catenin and epithelial-mesenchymal transition (EMT). These FOLFOX biomarker genes include the pyrimidine biosynthesis pathway genes dihydropyrimidine dehydrogenase (DPYD), thymidylate synthase (TYMS), methylenetetrahydrofolate reductase (MTHFR), and the genes encoding the DNA repair complexes subunits ERCC1 and ERCC2, and XRCC1. Methods: To assess this, we transfected SW480 and SW620 colon cancer cell lines with miR-92a-3p mimics and then quantified the expression of DPYD, TYMS, MTHFR, ERCC1, ERCC2, and XRCC1, the expression of EMT markers and transcription factors, and activation of β-catenin. Results and discussion: Our results reveal that miR-92a-3p does not affect the expression of DPYD, TYMS, MTHFR, and ERCC1. Furthermore, even though miR-92a-3p affects ERCC2, XRCC1, E-cadherin, and β-catenin mRNA levels, it has no influence on their protein expression. Conclusion: We found that miR-92a-3p does not upregulate the expression of proteins of DNA-repair pathways and other genes involved in FOLFOX chemotherapy resistance.
摘要：
简介：随着疾病的发展，晚期结直肠癌（CRC）患者面临的主要障碍之一是获得性化学耐药性的潜在发展。研究表明，miR-92a-3p水平升高与进展之间存在直接关联，转移,以及在CRC中观察到的化学耐药。我们提出miR-92a-3p通过激活β-catenin和上皮-间质转化（EMT）来上调化疗耐药生物标志物基因的表达，从而损害FOLFOX（氟尿嘧啶/奥沙利铂）化疗反应。这些FOLFOX生物标志物基因包括嘧啶生物合成途径基因二氢嘧啶脱氢酶（DPYD），胸苷酸合成酶（TYMS），亚甲基四氢叶酸还原酶（MTHFR），和编码DNA修复复合物亚基ERCC1和ERCC2以及XRCC1的基因。方法：为了评估这一点，我们用miR-92a-3p模拟物转染SW480和SW620结肠癌细胞系，然后定量DPYD的表达，TYMS,MTHFR,ERCC1、ERCC2和XRCC1，EMT标记和转录因子的表达，和β-连环蛋白的激活。结果与讨论：我们的结果表明miR-92a-3p不影响DPYD的表达，TYMS,MTHFR,和ERCC1。此外，即使miR-92a-3p影响ERCC2，XRCC1，E-cadherin，和β-连环蛋白mRNA水平，它对它们的蛋白质表达没有影响。结论：我们发现miR-92a-3p并不上调涉及FOLFOX化疗耐药的DNA修复通路蛋白和其他基因的表达。
