Lu Can, Chen Xi, Yan Yuanliang, Ren Xinxin, Wang Xiang, Peng Bi, Cai Yuan, Liang Qiuju, Xu Zhijie, Peng Jinwu
Department of Pathology, Xiangya Hospital, Central South University, Changsha, China.
Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, China.
Front Pharmacol. 2022 Feb 1;13:768743. doi: 10.3389/fphar.2022.768743. eCollection 2022.
Chemoresistance, especially temozolomide (TMZ) resistance, is a major clinical challenge in the treatment of glioblastoma (GBM). Exploring the mechanisms of TMZ resistance could help us identify effective therapies. Adenosine deaminases acting on RNA (ADARs) are very important in RNA modification through regulating the A-to-I RNA editing. Recent studies have shown that ADARs regulate multiple neurotransmitter receptors, which have been linked with the occurrence and progress of GBM. Here, data from several bioinformatics databases demonstrated that adenosine deaminase RNA specific B1 (ADARB1), also named ADAR2, was upregulated in both GBM tissues and cells, and had the prognostic value in GBM patients. Moreover, ADARB1 was found to be involved in AKT-mediated TMZ resistance in GBM cells. The KEGG analysis of ADARB1-associated co-expressed genes showed that ADARB1 was potentially involved in the mitochondrial respiratory chain complex. TISIDB and GEPIA databases were further used to analyze the role of ADARB1 in tumor-immune system interactions in GBM. These findings deepened our understanding of the function of ADARB1 in tumorigenesis and therapeutic response in GBM.
化疗耐药，尤其是对替莫唑胺（TMZ）的耐药，是胶质母细胞瘤（GBM）治疗中的一项重大临床挑战。探索TMZ耐药机制有助于我们确定有效的治疗方法。作用于RNA的腺苷脱氨酶（ADARs）通过调节A到I的RNA编辑在RNA修饰中非常重要。最近的研究表明，ADARs调节多种神经递质受体，这些受体与GBM的发生和进展有关。在这里，来自多个生物信息学数据库的数据表明，腺苷脱氨酶RNA特异性B1（ADARB1），也称为ADAR2，在GBM组织和细胞中均上调，并且对GBM患者具有预后价值。此外，发现ADARB1参与GBM细胞中AKT介导的TMZ耐药。对与ADARB1相关的共表达基因进行KEGG分析表明，ADARB1可能参与线粒体呼吸链复合体。进一步使用TISIDB和GEPIA数据库分析ADARB1在GBM肿瘤-免疫系统相互作用中的作用。这些发现加深了我们对ADARB1在GBM肿瘤发生和治疗反应中功能的理解。
