Hypermethylation of PRKCZ Regulated by E6 Inhibits Invasion and EMT Via Cdc42 in HPV-Related Head and Neck Squamous Cell Carcinoma

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2022 Sep 9

PMID 36077689

Authors

Hao-Fan Wang

Jian Jiang

Jia-Shun Wu

Mei Zhang

Xin Pang

Li Dai

Ya-Ling Tang

Xin-Hua Liang

Affiliations

Soon will be listed here.

Abstract

Purpose: To study the role of target genes with aberrant DNA methylation in HPV+ HNSCC.

Methods: A HumanMethylation450 BeadChip array (Illumina) was used to identify differentially methylated genes. CCK-8, flow cytometry, wound healing, and cell invasion assays were conducted to analyze the biological roles of PRKCZ. Western blot, qRT-PCR, immunohistochemistry, and animal studies were performed to explore the mechanisms underlying the functions of PRKCZ.

Results: We selected PRKCZ, which is associated with HPV infection, as our target gene. PRKCZ was hypermethylated in HPV+ HNSCC patients, and PRKCZ methylation status was negatively related to the pathological grading of HNSCC patients. Silencing PRKCZ inhibited the malignant capacity of HPV+ HNSCC cells. Mechanistically, HPV might promote DNMT1 expression via E6 to increase PRKCZ methylation. Cdc42 was required for the PRKCZ-mediated mechanism of action, contributing to the occurrence of epithelial-mesenchymal transition (EMT) in HPV+ HNSCC cells. In addition, blocking PRKCZ delayed tumor growth in HPV16-E6/E7 transgenic mice. Cdc42 expression was decreased, whereas E-cadherin levels increased.

Conclusion: We suggest that PRKCZ hypermethylation induces EMT via Cdc42 to act as a potent tumor promoter in HPV+ HNSCC.

Citing Articles

The Role of the Cytoskeletal Regulatory Protein, Mammalian Enabling Protein (Mena), in Invasion and Metastasis of HPV16-Related Oral Squamous Cell Carcinoma.

Guo Z, Xie L, Cui H, Yang X, Qi H, Yu M Cells. 2024; 13(23).

PMID: 39682720 PMC: 11640048. DOI: 10.3390/cells13231972.

Genetic polymorphism in untranslated regions of PRKCZ influences mRNA structure, stability and binding sites.

Mustafa A, Shabbir M, Badshah Y, Khan K, Abid F, Trembley J BMC Cancer. 2024; 24(1):1147.

PMID: 39272077 PMC: 11401371. DOI: 10.1186/s12885-024-12900-8.

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