ELK4 induced upregulation of HOMER3 promotes the proliferation and metastasis in glioma via Wnt/β-catenin/EMT signaling pathway.

in Biology direct by Furong Wang, Hui Zhou, Yu Tian, Xiaoling Wang, Youcai Huang, Yanyang Tu, Liwen Li, Haining Zhen

TLDR

  • The study found that HOMER3 is a potential prognostic biomarker and therapeutic target in glioma management, particularly for LGG patients.
  • Elevated HOMER3 expression was associated with poor prognosis and clinical progression in LGG patients.
  • The study highlights the potential for HOMER3-targeted therapies in glioma treatment and management.

Abstract

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.

Overview

  • The study aimed to investigate the expression profiles of the HOMER family in various cancers, including glioma, to understand their specific roles and identify potential biomarkers.
  • The study utilized data from public databases such as TCGA and GTEx to evaluate the expression profiles of HOMER family members across different tumor types.
  • The primary objective of the study was to identify potential prognostic biomarkers and therapeutic targets in glioma management, particularly for lower-grade glioma (LGG) patients.

Comparative Analysis & Findings

  • The study found significant dysregulation of HOMER1, HOMER2, and HOMER3 in multiple cancers, with HOMER3 emerging as a potential prognostic biomarker for LGG patients.
  • Elevated expression levels of HOMER3 were associated with shorter overall survival and disease-specific survival in LGG patients, supported by Cox regression analysis.
  • HOMER3 expression correlated positively with advanced clinical stages and key tumor markers, highlighting its potential role as a prognostic biomarker.

Implications and Future Directions

  • The study's findings suggest that HOMER3 plays a crucial role in glioma progression and metastasis, making it a potential therapeutic target in glioma management.
  • Future studies could investigate the mechanisms underlying HOMER3 dysregulation, including its transcriptional regulation by ELK4 and its effects on the Wnt/β-catenin/EMT signaling pathway.
  • The identification of HOMER3 as a potential prognostic biomarker and therapeutic target may lead to the development of novel treatments for glioma patients, especially those with LGG.
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