SET protein modulates H4 histone methylation status and regulates miR-137 level in oral squamous cell carcinoma

Author(s)

Sousa, Lucas Oliveira ^{[1, 2]} ; Sobral, Lays Martin ^[2] ; de Almeida, Luciana Oliveira ^[3] ; Garcia, Cristiana Bernadelli ^[2] ; Greene, Lewis Joel ^{[1, 4]} ; Leopoldino, Andreia Machado ^{[2, 4]}

Affiliation

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Cell & Mol Biol & Pathogen Bioagents, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Clin Anal Toxicol & Food Sci, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Sch Dent Ribeirao Preto, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Ribeirao Preto Med Sch, Reg Blood Ctr Ribeirao Preto, CEPID CTC, Sao Paulo - Brazil

• Document type: Journal article
• Source: Epigenomics; v. 12, n. 6, p. 475-485, MAR 2020.
• Web of Science Citations: 0

Abstract

Aim: Histone acetylation and methylation control gene expression. We investigated the impact of SET knockdown on histone methylation status and the consequences for the miRNAs levels in oral squamous cell carcinoma (OSCC). Methods: OSCC cells with and without SET knockdown were analyzed by quantitative real-time PCR to determine miRNA levels, and by immunoreactions to histone modifications. Results: The knockdown of SET increased the levels of histone H4K20me2 and miR-137. Still, SET protein binds to the miR-137 promoter region. The transfection of miR-137 mimic reduced the KI67 and Rb proteins and proliferation of OSCC cells. Conclusion: Our results show for the first time a relationship between SET and histone methylation associated with the control of miRNA expression and KI67 and Rb as targets of miR-137 in OSCC. (AU)

• FAPESP's process: 10/20384-0 - Identification of genes, miRNAs and proteins regulated by set oncoprotein and associated on malignization and tumor progression in HNSCC using in vitro and in vivo models
• Grantee: Andréia Machado Leopoldino
• Support Opportunities: Regular Research Grants
• FAPESP's process: 16/19103-2 - SET and sphingolipids in head and neck squamous cell carcinoma: signaling, targets and antiumoral therapy
• Grantee: Andréia Machado Leopoldino
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 13/10898-4 - Study of the molecular mechanisms by protein SET with impact on tumorigenesis and progression of oral cancer
• Grantee: Carlos Curti
• Support Opportunities: Regular Research Grants
• FAPESP's process: 13/08135-2 - CTC - Center for Cell-Based Therapy
• Grantee: Dimas Tadeu Covas
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC