SET Protein Modulates H4 Histone Methylation Status and Regulates miR-137 Level in Oral Squamous Cell Carcinoma

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.

Keywords::

• histones
• methylation
• miR-137
• OSCC
• SET/I2PP2A

Financial & competing interests disclosure

This study was financed in part by The Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brazil (CAPES) – Finance code 001, Conselho Nacional de Pesquisa e Tecnologia/CNPq, and Fundação de Amparo à Pesquisa do Estado de São Paulo/FAPESP (research grants #2010/20384-0; #2013/10898-4; #2016/19103-2 and CEPID: #2013/08135-2), Brazil. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This study was financed in part by The Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brazil (CAPES) – Finance code 001, Conselho Nacional de Pesquisa e Tecnologia/CNPq, and Fundação de Amparo à Pesquisa do Estado de São Paulo/FAPESP (research grants #2010/20384-0; #2013/10898-4; #2016/19103-2 and CEPID: #2013/08135-2), Brazil. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.