PRMT6-mediated Transcriptional Activation of Ythdf2 Promotes Glioblastoma Migration, Invasion, and Emt Via the Wnt-β-catenin Pathway

Overview

Journal J Exp Clin Cancer Res

Publisher Biomed Central

Specialty Oncology

Date 2024 Apr 18

PMID 38637831

Authors

Peng Yu

Tutu Xu

Wenmeng Ma

Xiang Fang

Yue Bao

Chengran Xu

Jinhai Huang

Yongqing Sun

Guangyu Li

Affiliations

Soon will be listed here.

Abstract

Background: Protein arginine methyltransferase 6 (PRMT6) plays a crucial role in various pathophysiological processes and diseases. Glioblastoma (GBM; WHO Grade 4 glioma) is the most common and lethal primary brain tumor in adults, with a prognosis that is extremely poor, despite being less common than other systemic malignancies. Our current research finds PRMT6 upregulated in GBM, enhancing tumor malignancy. Yet, the specifics of PRMT6's regulatory processes and potential molecular mechanisms in GBM remain largely unexplored.

Methods: PRMT6's expression and prognostic significance in GBM were assessed using glioma public databases, immunohistochemistry (IHC), and immunoblotting. Scratch and Transwell assays examined GBM cell migration and invasion. Immunoblotting evaluated the expression of epithelial-mesenchymal transition (EMT) and Wnt-β-catenin pathway-related proteins. Dual-luciferase reporter assays and ChIP-qPCR assessed the regulatory relationship between PRMT6 and YTHDF2. An in situ tumor model in nude mice evaluated in vivo conditions.

Results: Bioinformatics analysis indicates high expression of PRMT6 and YTHDF2 in GBM, correlating with poor prognosis. Functional experiments show PRMT6 and YTHDF2 promote GBM migration, invasion, and EMT. Mechanistic experiments reveal PRMT6 and CDK9 co-regulate YTHDF2 expression. YTHDF2 binds and promotes the degradation of negative regulators APC and GSK3β mRNA of the Wnt-β-catenin pathway, activating it and consequently enhancing GBM malignancy.

Conclusions: Our results demonstrate the PRMT6-YTHDF2-Wnt-β-Catenin axis promotes GBM migration, invasion, and EMT in vitro and in vivo, potentially serving as a therapeutic target for GBM.

Citing Articles

The YTH domain-containing protein family: Emerging players in immunomodulation and tumour immunotherapy targets.

Li F, Zeng C, Liu J, Wang L, Yuan X, Yuan L Clin Transl Med. 2024; 14(8):e1784.

PMID: 39135292 PMC: 11319238. DOI: 10.1002/ctm2.1784.

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