Determination of potential epigenetic therapeutic targets in non-small cell lung cancer

Apesar dos avanços nas abordagens diagnósticas e terapêuticas, muitos pacientes com câncer de pulmão ainda evoluem para estágios avançados com lesões metastáticas e óbito. Assim, novas terapias visando mecanismos epigenéticos relacionados aos processos metastáticos são muito importantes para o controle de genes específicos do câncer. Neste estudo, selecionamos uma pequena biblioteca de inibidores epigenéticos em linhagens de células de câncer de pulmão de células não- pequenas (CPCNP) e avaliamos 38 potenciais alvos epigenéticos no CPCNP metastático. Os potenciais candidatos foram classificados por uma abordagem simplificada usando experimentos in silico e in vitro com base em bancos de dados publicamente disponíveis e avaliados por expressão do gene alvo qPCR em tempo real, ensaios de viabilidade celular e invasão, e análise transcriptômica. A taxa de sobrevida dos pacientes com adenocarcinoma pulmonar é inversamente correlacionada com a expressão gênica de oito potenciais alvos epigenéticos, e uma revisão sistemática da literatura confirmou que quatro deles já foram identificados como alvos para o tratamento do CPCNP. Usando doses não citotóxicas dos inibidores selecionados, KDM6A/B (lysine demethylase 6A e 6B) e PADI4 (protein-arginine deiminase Type-4) foi avaliado que ambos afetam a atividade de invasão e migração de linhagens de células de câncer de pulmão metastático. A análise transcriptômica das células tratadas com KDM6A/B e PADI4 mostrou expressão alterada de genes importantes relacionados ao processo metastático. Em conclusão, mostramos que KDM6B e PADI4 são alvos promissores para inibir a metástase de células tumorais de adenocarcinoma pulmonar.Despite advances in diagnostic and therapeutic approaches for lung cancer, many patients still progress to advanced stages, with metastatic lesions and death. Thus, new therapies targeting metastasis by the specific regulation of cancer genes are needed. In this study, we screened a small library of epigenetic inhibitors in non-small-cell lung cancer (NSCLC) cell lines and evaluated 38 potential epigenetic targets for their role in metastatic NSCLC. The potential candidates were ranked by a streamlined approach using in silico and in vitro experiments based on publicly available databases, and evaluated by real-time qPCR target gene expression, cell viability and invasion assays, and transcriptomic analysis. The survival rate of patients with lung adenocarcinoma is inversely correlated with the gene expression of eight potential epigenetic targets, and a systematic review of the literature confirmed that four of them have already been identified as targets for the treatment of NSCLC. Using nontoxic doses of the remaining inhibitors, KDM6A/B (lysine demethylase 6A e 6B) and PADI4 (protein-arginine deiminase Type-4) were identified as potential targets affecting the invasion and migration of metastatic lung cancer cell lines. Transcriptomic analysis of KDM6A/B and PADI4 treated cells showed altered expression of important genes related to the metastatic process. In conclusion, we showed that KDM6B and PADI4 are promising targets for inhibiting the metastasis of lung adenocarcinoma cancer cells

A Screening of Epigenetic Therapeutic Targets for Non-Small Cell Lung Cancer Reveals PADI4 and KDM6B as Promising Candidates

Despite advances in diagnostic and therapeutic approaches for lung cancer, new therapies targeting metastasis by the specific regulation of cancer genes are needed. In this study, we screened a small library of epigenetic inhibitors in non-small-cell lung cancer (NSCLC) cell lines and evaluated 38 epigenetic targets for their potential role in metastatic NSCLC. The potential candidates were ranked by a streamlined approach using in silico and in vitro experiments based on publicly available databases and evaluated by real-time qPCR target gene expression, cell viability and invasion assays, and transcriptomic analysis. The survival rate of patients with lung adenocarcinoma is inversely correlated with the gene expression of eight epigenetic targets, and a systematic review of the literature confirmed that four of them have already been identified as targets for the treatment of NSCLC. Using nontoxic doses of the remaining inhibitors, KDM6B and PADI4 were identified as potential targets affecting the invasion and migration of metastatic lung cancer cell lines. Transcriptomic analysis of KDM6B and PADI4 treated cells showed altered expression of important genes related to the metastatic process. In conclusion, we showed that KDM6B and PADI4 are promising targets for inhibiting the metastasis of lung adenocarcinoma cancer cells

Correction: Lesbon et al. Nucleocapsid (N) Gene Mutations of SARS-CoV-2 Can Affect Real-Time RT-PCR Diagnostic and Impact False-Negative Results. <i>Viruses</i> 2021, <i>13</i>, 2474

The authors hereby request the inclusion of two authors (Olivia Teixeira and Maria Cristina Nonato) in the recently published article in Viruses entitled “Nucleocapsid (N) gene mutations of SARS-CoV-2 can affect real-time RT-PCR diagnostic and impact false-negative results” [...