Hypoxia-induced heterogeneity in colorectal cancer (CRC) significantly impacts patient survival by promoting chemoresistance. These conditions alter the regulation of miRNAs, key regulators of crucial processes like proliferation, apoptosis, and invasion, leading to tumor progression. Despite their promising potential as diagnostic and therapeutic targets, the underlying mechanisms by which miRNAs influence hypoxia-mediated tumorigenesis remain largely unexplored. This study aims to elucidate the action of miRNAs in HCT-116 colorectal cancer stem cells (CSCs) under hypoxia, providing valuable insights into their role in tumor adaptation and progression. MiRNA expression was determined using Nanostring nCounter, and bioinformatic analysis was performed to explain the molecular pathway. A total of 50 miRNAs were obtained with an average count of ≥ 20 reads for comparative expression analysis. The results showed that hypoxia-affected 36 oncomiRs were increased in HCT-116, and 14 suppressor-miRs were increased in MSCs. The increase in miRNA expression occurred consistently from normoxia to hypoxia and significantly differed between mesenchymal stem cells (MSCs) and HCT-116. Furthermore, miR-16-5p and miR-29a-3p were dominant in regulating the p53 signaling pathway, which is thought to be related to the escape mechanism against hypoxia and maintaining cell proliferation. More research with a genome-transcriptome axis approach is needed to fully understand miRNAs’ role in adapting CRC cells and MSCs to hypoxia. Further research could focus on developing specific biomarkers for diagnosis. In addition, anti-miR can be developed as a therapy to prevent cancer proliferation or inhibit the adaptation of cancer cells to hypoxia.

中文翻译：

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oncomiR 抑制缺氧条件结肠癌细胞系 HCT-116 中 TP53 信号通路的预测作用


缺氧诱导的结直肠癌 （CRC） 异质性通过促进化疗耐药性显着影响患者生存。这些条件改变了 miRNA 的调节，而 miRNA 是增殖、凋亡和侵袭等关键过程的关键调节因子，导致肿瘤进展。尽管它们作为诊断和治疗靶点具有广阔的潜力，但 miRNA 影响缺氧介导的肿瘤发生的潜在机制在很大程度上仍未得到探索。本研究旨在阐明 miRNAs 在缺氧条件下 HCT-116 结直肠癌干细胞 （CSCs） 中的作用，为它们在肿瘤适应和进展中的作用提供有价值的见解。使用 Nanostring nCounter 测定 MiRNA 表达，并进行生物信息学分析以解释分子途径。总共获得 50 个 miRNA，平均计数为 ≥ 20 个读数，用于比较表达分析。结果显示，受缺氧影响的 36 个 oncomiR 在 HCT-116 中增加，在 MSCs 中增加 14 个抑制因子 miR。miRNA 表达的增加从常氧到缺氧始终发生，并且间充质干细胞 （MSCs） 和 HCT-116 之间存在显著差异。此外，miR-16-5p 和 miR-29a-3p 在调节 p53 信号通路中占主导地位，这被认为与对抗缺氧和维持细胞增殖的逃逸机制有关。需要对基因组-转录组轴方法进行更多研究，以充分了解 miRNA 在使 CRC 细胞和 MSC 适应缺氧方面的作用。进一步的研究可以集中在开发用于诊断的特异性生物标志物上。此外，抗 miR 可以开发为一种疗法，以防止癌症增殖或抑制癌细胞对缺氧的适应。