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肺腺癌中低 ADARB1 表达的功能。

Function of low ADARB1 expression in lung adenocarcinoma.

机构信息

Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, Hunan, China.

National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China.

出版信息

PLoS One. 2019 Sep 6;14(9):e0222298. doi: 10.1371/journal.pone.0222298. eCollection 2019.

Abstract

Adenosine deaminase RNA-specific B1 (ADARB1), an adenosine-to-inosine (A-to-I) RNA-editing enzyme, has been found to play an essential role in the development of cancer. However, the specific function of ADARB1 in lung cancer, especially in lung adenocarcinoma (LUAD), is still not fully understood and requires further study. In our study, integrative bioinformatics were used to analyze the detailed function of ADARB1 in LUAD. By conducting bioinformatics analyses of several public databases, such as Gene Expression Profiling Interactive Analysis (GEPIA), GE-mini, and Oncomine, we found significantly decreased ADARB1 expression in LUAD cells and tissues. Moreover, RT-PCR and Western blot showed lower ADARB1 expression in H358 and A549 LUAD cells compared to human bronchial epithelial Beas-2B cells. Wound Healing Assay indicated that knockdown ADARB1 could promote LUAD cell metastasis. By using the Kaplan-Meier Plotter tool, we found that downregulation of ADARB1 was related to shorter first progression (FP), overall survival time (OS) and post-progression survival time (PPS). The relevant clinical data acquired from the Wanderer database indicated that the expression and methylation values of ADARB1 were significantly associated with the clinical characteristics of LUAD. Using DNA methylation inhibitor, we found DNMT inhibitor 5-aza-2-deoxycytidine (5-azaD) could promote the expression of ADARB1 and reverse the inhibition effect of ADARB1 in migration. In addition, functional enrichment analysis of ADARB1-associated coexpression genes was further conducted. Our investigation demonstrated that low levels of ADARB1 were specifically found in LUAD, and this gene might be a potential target in the diagnostic and prognostic evaluation of LUAD patients.

摘要

腺苷脱氨酶 RNA 特异性 B1(ADARB1)是一种腺苷到肌苷(A-to-I)的 RNA 编辑酶,已被发现在癌症的发展中发挥重要作用。然而,ADARB1 在肺癌中的具体功能,特别是在肺腺癌(LUAD)中的具体功能仍不完全清楚,需要进一步研究。在我们的研究中,综合生物信息学被用于分析 ADARB1 在 LUAD 中的详细功能。通过对几个公共数据库(如基因表达谱交互式分析(GEPIA)、GE-mini 和 Oncomine)进行生物信息学分析,我们发现 LUAD 细胞和组织中 ADARB1 的表达明显降低。此外,RT-PCR 和 Western blot 显示,与人类支气管上皮细胞 Beas-2B 相比,H358 和 A549 LUAD 细胞中 ADARB1 的表达水平较低。伤口愈合试验表明,敲低 ADARB1 可以促进 LUAD 细胞转移。通过使用 Kaplan-Meier Plotter 工具,我们发现 ADARB1 的下调与较短的首次进展(FP)、总生存时间(OS)和进展后生存时间(PPS)有关。从 Wanderer 数据库获得的相关临床数据表明,ADARB1 的表达和甲基化值与 LUAD 的临床特征显著相关。使用 DNA 甲基化抑制剂,我们发现 DNA 甲基化抑制剂 5-氮杂-2-脱氧胞苷(5-azaD)可以促进 ADARB1 的表达,并逆转 ADARB1 在迁移中的抑制作用。此外,还进一步进行了 ADARB1 相关共表达基因的功能富集分析。我们的研究表明,ADARB1 在 LUAD 中特异性低表达,该基因可能是 LUAD 患者诊断和预后评估的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a0f4/6730894/5fe50276c71f/pone.0222298.g001.jpg

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