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Differential regulation of LRRC37A2 in gastric cancer by DNA methylation

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Wisnieski, Fernanda ; Geraldis, Jaqueline Cruz ; Santos, Leonardo Caires ; Leal, Mariana Ferreira ; Calcagno, Danielle Queiroz ; Gigek, Carolina Oliveira ; Chen, Elizabeth Suchi ; Anauate, Ana Carolina ; Artigiani, Ricardo ; Demachki, Samia ; Assumpcao, Paulo Pimentel ; Lourenco, Laercio Gomes ; Arasaki, Carlos Haruo ; Krainer, Julie ; Pabinger, Stephan ; Burbano, Rommel Rodriguez ; Cardoso Smith, Marilia Arruda
Número total de Autores: 17
Tipo de documento: Artigo Científico
Fonte: Epigenetics; v. 17, n. 1, p. 7-pg., 2021-02-07.
Resumo

Gastric cancer (GC) is one of the leading types of fatal cancer worldwide. Epigenetic manipulation of cancer cells is a useful tool to better understand gene expression regulatory mechanisms and contributes to the discovery of novel biomarkers. Our research group recently reported a list of 83 genes that are potentially modulated by DNA methylation in GC cell lines. Herein, we further explored the regulation of one of these genes, LRRC37A2, in clinical samples. LRRC37A2 expression was evaluated by RT-qPCR, and DNA methylation was studied using next-generation bisulphite sequencing in 36 GC and paired adjacent nonneoplastic tissue samples. We showed that both reduced LRRC37A2 mRNA levels and increased LRRC37A2 exon methylation were associated with undifferentiated and poorly differentiated tumours. Moreover, LRRC37A2 gene expression and methylation levels were inversely correlated at the +45 exon CpG site. We suggest that DNA hypermethylation may contribute to reducing LRRC37A2 expression in undifferentiated and poorly differentiated GC. Therefore, our results show how some genes may be useful to stratify patients who are more likely to benefit from epigenetic therapy. (AU)

Processo FAPESP: 07/02470-3 - Análise fosfo e glico proteômica diferencial em adenocarcinoma gástrico e sua eventual correlação com parâmetros clínico-patológicos de prognóstico
Beneficiário:Mariana Ferreira Leal
Modalidade de apoio: Bolsas no Brasil - Doutorado
Processo FAPESP: 17/06227-8 - Análise da metilação de DNA na compreensão da regulação transcricional de genes relevantes na carcinogênese gástrica
Beneficiário:Jaqueline Cruz Geraldis
Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
Processo FAPESP: 09/07145-9 - Aspectos genéticos e epigenéticos na carcinogênese gástrica
Beneficiário:Marilia de Arruda Cardoso Smith
Modalidade de apoio: Auxílio à Pesquisa - Temático
Processo FAPESP: 10/11174-1 - Avaliação genética e epigenética no câncer gástrico
Beneficiário:Danielle Queiroz Calcagno
Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
Processo FAPESP: 16/19953-6 - Genes modulados epigeneticamente poderão constituir alvos terapêuticos em pacientes com câncer gástrico?
Beneficiário:Fernanda Wisnieski
Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado