Medical School, Graduate Section, National Polytechnic Institute, Mexico City, Mexico.
Department of Biomedicine, Faculty of Medicine, Meritorious Autonomous University of Puebla (BUAP), Puebla, Mexico.
Adv Clin Exp Med. 2021 May;30(5):507-515. doi: 10.17219/acem/133426.
Plant homeodomain finger protein 20-like 1 (PHF20L1) is a protein reader involved in epigenetic regulation that binds monomethyl-lysine. An oncogenic function has been attributed to PHF20L1 but its role in breast cancer (BC) is not clear.
To explore PHF20L1 promoter methylation and comprehensive bioinformatics analysis to improve understanding of the role of PHF20L1 in BC.
Seventy-four BC samples and 16 control samples were converted using sodium bisulfite treatment and analyzed with methylation-specific polymerase chain reaction (PCR). Bioinformatic analysis was performed in the BC dataset using The Cancer Genome Atlas (TCGA) trough data visualized and interpreted in the MEXPRESS website. Methylation, gene expression and survival evaluation were performed with R v. 4.0.2 software. Using multiple bioinformatic tools, we conducted a search for genes co-expressed with PHF20L1, analyzed its ontology and predicted associated miRNAs and miRNA-PHF20L1 networks. The expression and prognostic value of PHF20L1 and co-expressed genes were analyzed.
We found demethylation in PHF20L1 promoter in both BC samples and healthy tissues. Data mining with 241 patients demonstrated changes in methylation of promoter regions in basal-like and luminal A subtypes. Expression of the PHF20L1 gene had a negative correlation with methylation. Twelve genes were co-expressed. PHF20L1 is a target of miR96-5p, miR9-5p and miR182-5p, which are involved in proliferation and metastasis. PHF20L1 gene expression was not associated with overall survival (OS), or relapse-free survival (RFS), but was associated with distant metastasis-free survival (DMFS).
Our findings showed differences in methylation of PHF20L1 promoter region near TSS and upstream in BC subtypes; its overexpression impacted DMFS. We found that PHF20L1 is targeted by miR96-5p, miR9-5p and miR182-5p, which are involved in proliferation and metastasis, and regulates genes engaged in processes such as alternative splicing.
植物同源结构域指蛋白 20 样 1（PHF20L1）是一种参与表观遗传调控的蛋白阅读因子，可与单甲基化赖氨酸结合。PHF20L1 具有致癌功能，但在乳腺癌（BC）中的作用尚不清楚。
探索 PHF20L1 启动子甲基化，并进行综合生物信息学分析，以提高对 PHF20L1 在 BC 中作用的认识。
采用亚硫酸氢盐处理将 74 例 BC 样本和 16 例对照样本进行转化，并用甲基化特异性聚合酶链反应（PCR）进行分析。利用 The Cancer Genome Atlas（TCGA）的转录组数据，在 MEXPRESS 网站上进行可视化和解释，在 BC 数据集进行生物信息学分析。采用 R v.4.0.2 软件进行甲基化、基因表达和生存评估。使用多种生物信息学工具，我们进行了与 PHF20L1 共表达基因的搜索，分析了它们的本体，并预测了相关的 miRNA 和 miRNA-PHF20L1 网络。分析了 PHF20L1 和共表达基因的表达和预后价值。
我们发现 BC 样本和健康组织中 PHF20L1 启动子去甲基化。对 241 例患者进行的数据挖掘显示，基底样和管腔 A 型亚组中启动子区域的甲基化发生改变。PHF20L1 基因的表达与甲基化呈负相关。有 12 个基因共表达。PHF20L1 是 miR96-5p、miR9-5p 和 miR182-5p 的靶基因，这些 miRNA 参与增殖和转移。PHF20L1 基因表达与总生存期（OS）或无复发生存期（RFS）无关，但与无远处转移生存期（DMFS）有关。
我们的研究结果表明，BC 亚型中 PHF20L1 启动子区域靠近 TSS 和上游的甲基化存在差异；其过表达影响 DMFS。我们发现，PHF20L1 是 miR96-5p、miR9-5p 和 miR182-5p 的靶基因，这些 miRNA 参与增殖和转移，并调节参与选择性剪接等过程的基因。
