Liu Yuhang, Zhang Hao, Yi Xinzeyu, Wang Zheng, Yu Aixi
Department of trauma and microorthopaedics, Zhongnan Hospital of Wuhan University, Wuhan, China.
J Cell Mol Med. 2025 Jun;29(12):e70042. doi: 10.1111/jcmm.70042.
Osteosarcoma (OS) is a highly prevalent and deadly malignant tumour primarily affecting adolescents. However, the identification of new therapeutic targets remains an urgent need. The advent of bioinformatics technology has offered us a novel approach to screen key genes from diverse OS-related databases, thereby providing valuable insights into the mechanistic understanding of OS prognosis. In this study, we comprehensively integrated multiple databases to identify the crucial oncogene, HEY1, which exerts a significant impact on OS prognosis. Subsequently, we conducted a experimental validations to explore influence of HEY1 knockdown on OS cells. HEY1 exhibited significant overexpression in OS tissues and cells and its silencing resulted in a significant inhibition of proliferation. The interaction between HEY1 and CD44 was identified through transcriptome sequencing and mass spectrometry analysis. Additionally, our findings suggested that HEY1 could potentially influence the EGFR-FAK pathway. Further experiments established that HEY1 regulates the EGFR-FAK pathway via CD44, thereby influencing the biological phenotype of OS cells. These findings were subsequently validated using in vivo animal models. In summary, HEY1 demonstrated significant overexpression in both OS tissues and cells, exerting a substantial impact on the prognosis of OS.
骨肉瘤（OS）是一种主要影响青少年的高度常见且致命的恶性肿瘤。然而，识别新的治疗靶点仍然是一项迫切需求。生物信息学技术的出现为我们提供了一种从各种与OS相关的数据库中筛选关键基因的新方法，从而为深入理解OS预后的机制提供了有价值的见解。在本研究中，我们全面整合了多个数据库，以识别关键致癌基因HEY1，其对OS预后有重大影响。随后，我们进行了实验验证，以探究敲低HEY1对OS细胞的影响。HEY1在OS组织和细胞中显著过表达，其沉默导致增殖显著抑制。通过转录组测序和质谱分析确定了HEY1与CD44之间的相互作用。此外，我们的研究结果表明，HEY1可能影响EGFR-FAK通路。进一步的实验证实，HEY1通过CD44调节EGFR-FAK通路，从而影响OS细胞的生物学表型。随后使用体内动物模型验证了这些发现。总之，HEY1在OS组织和细胞中均显著过表达，对OS预后有重大影响。
