Wang Furong, Zhou Hui, Tian Yu, Wang Xiaoling, Huang Youcai, Tu Yanyang, Li Liwen, Zhen Haining
Department of Pathology, Huizhou Central People's Hospital, Huizhou, Guangdong, China.
Department of Pathology, Huizhou Central People's Hospital, Guangdong Medical University, Huizhou, China.
Biol Direct. 2025 Apr 9;20(1):48. doi: 10.1186/s13062-025-00643-w.
Glioma is an aggressive brain tumor characterized by its high invasiveness, which complicates prognosis and contributes to patient resistance against various treatment options. The HOMER family, consisting of HOMER1, HOMER2, and HOMER3, has been implicated in various cancers, yet their specific roles in glioma remain inadequately understood. This study conducted a comprehensive pan-cancer analysis to evaluate the expression profiles of HOMER family members across different tumor types, utilizing data from public databases such as TCGA and GTEx. Our findings indicate significant dysregulation of HOMER1, HOMER2, and HOMER3 in multiple cancers, with HOMER3 emerging as a potential prognostic biomarker, particularly for lower-grade glioma. Elevated expression levels of HOMER3 were associated with shorter overall survival and disease-specific survival in LGG patients, supported by Cox regression analysis that confirmed HOMER3 as an independent prognostic factor. Furthermore, HOMER3 expression correlated positively with advanced clinical stages and key tumor markers. To elucidate the mechanisms behind HOMER3 dysregulation, we identified ELK4 as a transcription factor that binds to the HOMER3 promoter, promoting its expression in glioma cells. Functional assays demonstrated that silencing HOMER3 significantly reduced glioma cell proliferation and metastatic potential in vitro and in vivo, highlighting its oncogenic role. Additionally, HOMER3 was found to influence the Wnt/β-catenin/EMT signaling pathway, with knockdown resulting in altered expression of critical EMT markers. Collectively, our results indicated that HOMER3 plays a crucial role in glioma progression and metastasis, underscoring its potential as a therapeutic target and prognostic biomarker in glioma management.
胶质瘤是一种侵袭性脑肿瘤，其特点是具有高侵袭性，这使得预后复杂化，并导致患者对各种治疗方案产生抗性。由HOMER1、HOMER2和HOMER3组成的HOMER家族与多种癌症有关，但其在胶质瘤中的具体作用仍未得到充分了解。本研究进行了全面的泛癌分析，利用来自TCGA和GTEx等公共数据库的数据，评估HOMER家族成员在不同肿瘤类型中的表达谱。我们的研究结果表明，HOMER1、HOMER2和HOMER3在多种癌症中存在显著失调，其中HOMER3成为一种潜在的预后生物标志物，特别是对于低级别胶质瘤。HOMER3表达水平升高与低级别胶质瘤（LGG）患者的总生存期和疾病特异性生存期缩短相关，Cox回归分析证实HOMER3是一个独立的预后因素。此外，HOMER3表达与晚期临床分期和关键肿瘤标志物呈正相关。为了阐明HOMER3失调背后的机制，我们确定ELK4是一种与HOMER3启动子结合的转录因子，可促进其在胶质瘤细胞中的表达。功能试验表明，沉默HOMER3可显著降低胶质瘤细胞在体外和体内的增殖和转移潜力，突出了其致癌作用。此外，发现HOMER3影响Wnt/β-连环蛋白/上皮-间质转化（EMT）信号通路，敲低导致关键EMT标志物的表达改变。总的来说，我们的结果表明HOMER3在胶质瘤进展和转移中起关键作用，强调了其作为胶质瘤治疗靶点和预后生物标志物的潜力。
