All India Institute of Medical Sciences, Jodhpur, Rajasthan, India.
Department of computer science and engineering, Indian Institute of Technology, Delhi, India.
Asian Pac J Cancer Prev. 2022 Mar 1;23(3):877-883. doi: 10.31557/APJCP.2022.23.3.877.
The present study aims to identify the effect of ZnHDACs expression on the survival of the patients. Further, reveal the unique and common genes associated with each ZnHDACs and their associated pathways.
The patient data was obtained from the Cancer Genome Atlas Program (TCGA) database and was analyzed using cBioportal and Gene Expression Profiling Interactive Analysis 2(GEPIA2) online tools. Protein-protein interactions and functional interactomic analysis were done using STRING, DAVID, and KEGG pathway databases.
HDAC1, 2, 8, 11 were over-expressed and, HDAC4, 5, 6, 7, and 10 were down-regulated in all the cancer types, but there are few exceptional expression patterns such as HDAC7 and HDAC10 overexpression in HNSC, HDAC3 down-regulation in LUAD, and PRAD. The unique genes interacting with each ZnHDACs provided a better understanding of ZnHDAC's putative role in carcinogenesis. The present study reported that JARID2, stem cell regulation gene uniquely interacts with HDAC1, BPTF-CHRAC-BAZIA axis, enzymes for chromatin modeling selectively interacting with only HDAC2, HDAC3 in H2A acetylation via DMAP1 and YEATS4. HDAC6 associated unique genes regulate protein stability, HDAC7 in subnuclear localization and splicing, HDAC8 in telomere maintenance, HDAC9 in chromosomal rearrangements, and HDAC11 in maintaining histone core and folding.
The unique genes and pathways associated with a particular ZnHDACs could provide a wide window for interrogating these genes for obtaining putative drug targets.
本研究旨在确定 ZnHDACs 表达对患者生存的影响。此外，揭示与每个 ZnHDACs 相关的独特和共同基因及其相关途径。
从癌症基因组图谱计划（TCGA）数据库中获取患者数据，并使用 cBioportal 和基因表达谱交互式分析 2（GEPIA2）在线工具进行分析。使用 STRING、DAVID 和 KEGG 途径数据库进行蛋白质-蛋白质相互作用和功能互作分析。
HDAC1、2、8、11 在所有癌症类型中均过表达，而 HDAC4、5、6、7 和 10 则下调，但也存在一些例外的表达模式，如 HNSC 中 HDAC7 和 HDAC10 的过表达、LUAD 中 HDAC3 的下调以及 PRAD 中 HDAC3 的下调。与每个 ZnHDACs 相互作用的独特基因提供了对 ZnHDAC 在致癌作用中潜在作用的更好理解。本研究报告称，JARID2、干细胞调节基因与 HDAC1 独特相互作用，BPTF-CHRAC-BAZIA 轴、仅与 HDAC2、HDAC3 选择性相互作用的染色质建模酶、通过 DMAP1 和 YEATS4 进行 H2A 乙酰化的 HDAC6 相关独特基因调节蛋白质稳定性、HDAC7 参与亚核定位和剪接、HDAC8 参与端粒维持、HDAC9 参与染色体重排、以及 HDAC11 参与维持组蛋白核心和折叠。
与特定 ZnHDACs 相关的独特基因和途径可以为研究这些基因以获得潜在的药物靶点提供广泛的窗口。
