Department of Radiation Oncology, The First Affiliated Hospital of Soochow University, Suzhou, China.
The Second People's Hospital of Changzhou, The Third Affiliated Hospital of Nanjing Medical University, Changzhou, China.
J Biochem Mol Toxicol. 2024 Nov;38(11):e70012. doi: 10.1002/jbt.70012.
Colorectal cancer (CRC) represents a substantial challenge to public health. Despite extensive research, the pathogenesis of CRC is not yet fully elucidated, hindering the development of effective therapeutic strategies. Recent advancements have underscored the importance of Non-coding RNAs in tumor biology. Our research identified a significant upregulation of Linc00475 in CRC, which correlated with reduced survival rates among CRC patients. Consequently, this study aimed to elucidate the mechanisms by which Linc00475 contributed to CRC progression. Employing a comprehensive array of experimental techniques-including CCK-8 assays, colony formation assays, flow cytometry, quantitative PCR (qPCR), western blot analysis, and in vivo tumorigenesis assays-we have demonstrated that Linc00475 enhances CRC cell proliferation. Further analysis revealed that Linc00475 directly interacted with miR-107, leading to its downregulation. Moreover, our findings confirmed that miR-107 directly targeted CDK6, which was markedly downregulated following Linc00475 silencing. In vivo experiments further indicated that the silencing of Linc00475 markedly inhibited the proliferation of CRC cells. Collectively, our findings suggested that Linc00475 facilitated CRC cell proliferation through the regulation of the miR-107/CDK6 axis, thereby providing a novel perspective for understanding the molecular mechanisms underlying CRC development.
结直肠癌（CRC）对公共健康构成了重大挑战。尽管进行了广泛的研究，但 CRC 的发病机制仍未完全阐明，这阻碍了有效治疗策略的发展。最近的进展强调了非编码 RNA 在肿瘤生物学中的重要性。我们的研究发现 Linc00475 在 CRC 中显著上调，这与 CRC 患者生存率降低有关。因此，本研究旨在阐明 Linc00475 促进 CRC 进展的机制。通过使用一系列全面的实验技术，包括 CCK-8 测定、集落形成测定、流式细胞术、定量 PCR（qPCR）、western blot 分析和体内肿瘤发生测定，我们证明了 Linc00475 增强了 CRC 细胞的增殖。进一步分析表明，Linc00475 与 miR-107 直接相互作用，导致其下调。此外，我们的研究结果证实，miR-107 直接靶向 CDK6，而 Linc00475 沉默后 CDK6 明显下调。体内实验进一步表明，Linc00475 的沉默显著抑制了 CRC 细胞的增殖。综上所述，我们的研究结果表明，Linc00475 通过调节 miR-107/CDK6 轴促进 CRC 细胞增殖，从而为理解 CRC 发展的分子机制提供了新的视角。
