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SFRP1 is a possible candidate for epigenetic therapy in non-small cell lung cancer

机译:SFRP1在非小细胞肺癌中可能是表观遗传学治疗的候选药物

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Background Non-small cell lung cancer (NSCLC) remains a lethal disease despite many proposed treatments. Recent studies have indicated that epigenetic therapy, which targets epigenetic effects, might be a new therapeutic methodology for NSCLC. However, it is not clear which objects (e.g., genes) this treatment specifically targets. Secreted frizzled-related proteins (SFRPs) are promising candidates for epigenetic therapy in many cancers, but there have been no reports of SFRPs targeted by epigenetic therapy for NSCLC. Methods This study performed a meta-analysis of reprogrammed NSCLC cell lines instead of the direct examination of epigenetic therapy treatment to identify epigenetic therapy targets. In addition, mRNA expression/promoter methylation profiles were processed by recently proposed principal component analysis based unsupervised feature extraction and categorical regression analysis based feature extraction. Results The Wnt/β-catenin signalling pathway was extensively enriched among 32 genes identified by feature extraction. Among the genes identified, SFRP1 was specifically indicated to target β-catenin, and thus might be targeted by epigenetic therapy in NSCLC cell lines. A histone deacetylase inhibitor might reactivate SFRP1 based upon the re-analysis of a public domain data set. Numerical computation validated the binding of SFRP1 to WNT1 to suppress Wnt signalling pathway activation in NSCLC. Conclusions The meta-analysis of reprogrammed NSCLC cell lines identified SFRP1 as a promising target of epigenetic therapy for NSCLC.
机译:背景技术尽管有许多建议的治疗方法,但非小细胞肺癌(NSCLC)仍然是致死性疾病。最近的研究表明,针对表观遗传效应的表观遗传疗法可能是NSCLC的一种新的治疗方法。但是,尚不清楚该治疗具体针对哪些对象(例如基因)。分泌的卷曲相关蛋白(SFRPs)是许多癌症中表观遗传学治疗的有前途的候选者,但尚无关于NSCLC的表观遗传学治疗靶向的SFRPs的报道。方法本研究对重新编程的NSCLC细胞系进行了荟萃分析,而不是直接检查表观遗传治疗方法以鉴定表观遗传治疗靶标。另外,通过最近提出的基于无监督特征提取的主成分分析和基于特征提取的分类回归分析来处理mRNA表达/启动子甲基化谱。结果Wnt /β-catenin信号通路在特征提取所鉴定的32个基因中广泛丰富。在鉴定出的基因中,SFRP1被特异性地靶向β-catenin,因此可能被NSCLC细胞系的表观遗传学治疗所靶向。基于对公共领域数据集的重新分析,组蛋白脱乙酰基酶抑制剂可能会重新激活SFRP1。数值计算验证了SFRP1与WNT1的结合以抑制NSCLC中Wnt信号通路的激活。结论对重新编程的NSCLC细胞系进行的荟萃分析确定SFRP1是NSCLC表观遗传治疗的有希望的靶标。

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