The allelic regulation of tumor suppressor ADARB2 in papillary thyroid carcinoma.

IF 4.1 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM Endocrine-related cancer Pub Date : 2023-01-01 DOI:10.1530/ERC-22-0189
Wenwen Li, Teng Wang, Guobin Fu, Yuan Xu, Nasha Zhang, Linyu Han, Ming Yang
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引用次数: 1

Abstract

Papillary thyroid cancer (PTC) is one of the histological subtypes of thyroid cancer which is the most common endocrine malignancy in the world. The disrupted balance of the adenosine-to-inosine (A-to-I) RNA editing due to dysregulation of the editing genes exists in thyroid cancer. However, it is still largely unknown how functional single-nucleotide polymorphisms (SNPs) in the A-to-I RNA editing genes contribute to PTC genetic susceptibility. In this study, we systematically annotated and investigated the role of 28 potential functional SNPs of ADAR, ADARB1, ADARB2 and AIMP2 in PTC. We identified ADARB2 rs904957 and rs1007147 genetic variants which are associated with significantly elevated PTC risk in two case-control sets consisting of 2020 PTC cases and 2021 controls. Further investigations disclosed that ADARB2 could inhibit cell viability and invasion capabilities of PTC cells as a novel tumor suppressor. The ADARB2 rs904957 thymine-to-cytosine (T-to-C) polymorphism in gene 3'-untranslated region enhances miR-1180-3p-binding affinity and represses ADARB2 expression through an allele-specific manner. In line with this, carriers with the rs904957 C allele correlated with decreased tumor suppressor ADARB2 expression in tissue specimens showed notably increased risk of developing PTC compared to the T allele carriers. Our findings highlight that the A-to-I RNA editing gene ADARB2 SNPs confer PTC risk. Importantly, these insights would improve our understanding for the general roles of RNA editing and editing genes during cancer development.

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肿瘤抑制因子ADARB2在甲状腺乳头状癌中的等位基因调控。
甲状腺乳头状癌(PTC)是甲状腺癌的组织学亚型之一,是世界上最常见的内分泌恶性肿瘤。甲状腺癌中存在由于编辑基因失调而导致的腺苷-肌苷(A-to-I) RNA编辑平衡被破坏。然而,A-to-I RNA编辑基因中的功能性单核苷酸多态性(snp)如何影响PTC的遗传易感性仍是一个很大的未知数。在这项研究中,我们系统地注释和研究了ADAR、ADARB1、ADARB2和AIMP2的28个潜在功能snp在PTC中的作用。我们在两个病例对照组(包括2020例PTC病例和2021例对照)中发现ADARB2 rs904957和rs1007147遗传变异与PTC风险显著升高相关。进一步的研究发现,ADARB2作为一种新的肿瘤抑制因子,可以抑制PTC细胞的细胞活力和侵袭能力。ADARB2基因3'-非翻译区rs904957胸腺嘧啶-胞嘧啶(T-to-C)多态性增强了mir -1180-3p结合亲和力,并通过等位基因特异性方式抑制ADARB2的表达。与此相一致的是,与组织标本中肿瘤抑制因子ADARB2表达降低相关的rs904957 C等位基因携带者与T等位基因携带者相比,发生PTC的风险显著增加。我们的研究结果强调,A-to-I RNA编辑基因ADARB2 snp会导致PTC风险。重要的是,这些见解将提高我们对RNA编辑和编辑基因在癌症发展过程中的一般作用的理解。
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来源期刊
Endocrine-related cancer
Endocrine-related cancer 医学-内分泌学与代谢
CiteScore
7.80
自引率
2.60%
发文量
138
审稿时长
6-12 weeks
期刊介绍: Endocrine-Related Cancer is an official flagship journal of the Society for Endocrinology and is endorsed by the European Society of Endocrinology, the United Kingdom and Ireland Neuroendocrine Society, and the Japanese Hormones and Cancer Society. Endocrine-Related Cancer provides a unique international forum for the publication of high quality original articles describing novel, cutting edge basic laboratory, translational and clinical investigations of human health and disease focusing on endocrine neoplasias and hormone-dependent cancers; and for the publication of authoritative review articles in these topics. Endocrine neoplasias include adrenal cortex, breast, multiple endocrine neoplasia, neuroendocrine tumours, ovary, prostate, paraganglioma, parathyroid, pheochromocytoma pituitary, testes, thyroid and hormone-dependent cancers. Neoplasias affecting metabolism and energy production such as bladder, bone, kidney, lung, and head and neck, are also considered.
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