低甲基化和由此产生的PARM1过表达:弥漫性大b细胞淋巴瘤预后不良的生物标志物。

IF 2 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Discovery medicine Pub Date : 2022-01-01
Baoping Cao, Xiaochuan Guo, Bin Wang, Weixia Wang, Dong Han, Weijing Zhang, Kaili Zhong
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引用次数: 0

摘要

前列腺雄激素调节的黏液样蛋白(PARM1)通过保护细胞表面促进细胞存活,从而参与癌症的发展。通过基因表达谱交互分析(GEPIA)、MEXPRESS数据库、LinkedOmics数据库、GeneMANIA数据库和Tumor Immune Estimation Resource (TIMER)数据库,探讨PARM1在弥漫性大b细胞淋巴瘤(DLBCL)中的表观遗传调控、预后价值、生物学功能和机制。在DLBCL中发现了低甲基化和由此产生的PARM1过表达。PARM1的高表达与DLBCL患者预后不良有关。PARM1参与DNA修复、细胞周期和细胞对应激的反应。PARM1还与自噬、凋亡、Ras通路和MAPK级联有关。PARM1的重要激酶靶点包括ATM、CDK1和CDK2。PARM1的重要转录因子靶点包括ELK1、MYC等。PARM1的重要miRNA靶点包括miR21、miR202、miR323和miR345。进一步分析表明,PARM1通过PI3K-Akt信号通路调控自噬。发现PARM1与免疫细胞浸润相关,提示PARM1在DLBCL微环境中的重要作用。本研究为进一步研究PARM1在DLBCL肿瘤发生及精准治疗中的作用奠定了基础。
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Hypomethylation and the Resultant Overexpressed PARM1: a Biomarker for Poor Prognosis of Diffuse Large B-cell Lymphoma.

Prostate androgen-regulated mucin-like protein (PARM1) is known to promote cell survival via protecting the cell surface, thus being involved in cancer development. The Gene Expression Profiling Interactive Analysis (GEPIA), MEXPRESS database, LinkedOmics database, GeneMANIA database, and the Tumor Immune Estimation Resource (TIMER) database were accessed to explore the epigenetic regulation, prognostic value, biological functions and mechanisms of PARM1 in diffuse large B-cell lymphoma (DLBCL). Hypomethylation and resultant overexpression of PARM1 was found in DLBCL. The high-level expression of PARM1 was related to the poor outcome of DLBCL patients. PARM1 participated in DNA repair, cell cycle, and cellular response to stress. PARM1 was also associated with autophagy, apoptosis, Ras pathway, and MAPK cascade. Significant kinase targets of PARM1 included ATM, CDK1, and CDK2. Significant transcription factor targets of PARM1 involved ELK1, MYC and so on. Significant miRNA targets of PARM1 included miR21, miR202, miR323, and miR345. Further analysis suggested that the PARM1 regulated autophagy through the PI3K-Akt signaling. PARM1 was found to be correlated with immune cell infiltration, which indicated the important roles of PARM1 in microenvironment of DLBCL. Our study lays a foundation for further research on the impact of PARM1 in DLBCL tumorigenesis and precision therapy.

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来源期刊
Discovery medicine
Discovery medicine MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
5.40
自引率
0.00%
发文量
80
审稿时长
6-12 weeks
期刊介绍: Discovery Medicine publishes novel, provocative ideas and research findings that challenge conventional notions about disease mechanisms, diagnosis, treatment, or any of the life sciences subjects. It publishes cutting-edge, reliable, and authoritative information in all branches of life sciences but primarily in the following areas: Novel therapies and diagnostics (approved or experimental); innovative ideas, research technologies, and translational research that will give rise to the next generation of new drugs and therapies; breakthrough understanding of mechanism of disease, biology, and physiology; and commercialization of biomedical discoveries pertaining to the development of new drugs, therapies, medical devices, and research technology.
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