miRNA 插入/缺失多态性与亚马孙人群胃癌易感性的关联。

Association between INDELs in MicroRNAs and Susceptibility to Gastric Cancer in Amazonian Population.

机构信息

Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, R. dos Mundurucus 4487, Guamá, Belém 66073-000, Brazil.

Laboratório de Genética Humana e Médica, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém 66073-000, Brazil.

出版信息

Genes (Basel). 2022 Dec 24;14(1):60. doi: 10.3390/genes14010060.

DOI:10.3390/genes14010060

PMID:36672804

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9858651/

Abstract

Gastric cancer (GC) is a multifactorial, complex, and aggressive disease with a prevalence of one million new cases and high global mortality. Factors such as genetic, epigenetic, and environmental changes contribute to the onset and progression of the disease. Identification of INDELs in miRNA and its target sites in current studies showed an important role in the development of cancer. In GC, miRNAs act as oncogenes or tumor suppressors, favoring important cancer pathways, such as cell proliferation and migration. This work aims to investigate INDELs in the coding region of miRNAs (hsa-miR-302c, hsa-miR-548AJ-2, hsa-miR-4274, hsa-miR-630, hsa-miR-516B-2, hsa-miR-4463, hsa-miR-3945, hsa-miR-548H_4, hsa-miR-920, has-mir-3171, and hsa-miR-3652) that may be associated with susceptibility and clinical variants of gastric cancer. For this study, 301 patients with GC and 145 individuals from the control group were selected from an admixed population in the Brazilian Amazon. The results showed the hsa-miR-4463, hsa-miR-3945, hsa-miR-548H_4, hsa-miR-920 and hsa-miR-3652 variants were associated with gastric cancer susceptibility. The hsa-miR-4463 was significantly associated with clinical features of GC such as diffuse gastric tumor histological type, "non-cardia" localization region, and early onset. Our findings indicated that INDELs could be potentially functional genetic variants for gastric cancer risk.

摘要

胃癌（GC）是一种多因素、复杂且侵袭性的疾病，全球每年新发胃癌病例超过 100 万，死亡率较高。遗传、表观遗传和环境因素的变化都可能导致该疾病的发生和发展。目前的研究表明，miRNA 中的 INDELs 及其靶位点的变化在癌症的发生发展中起着重要作用。在胃癌中，miRNA 可以作为癌基因或肿瘤抑制因子，促进细胞增殖和迁移等重要的癌症通路。本研究旨在探讨 miRNA 编码区的 INDELs（hsa-miR-302c、hsa-miR-548AJ-2、hsa-miR-4274、hsa-miR-630、hsa-miR-516B-2、hsa-miR-4463、hsa-miR-3945、hsa-miR-548H_4、hsa-miR-920、has-mir-3171 和 hsa-miR-3652）与胃癌易感性和临床变异的关系。为此，从巴西亚马逊地区的混合人群中选择了 301 例胃癌患者和 145 例对照组个体进行了这项研究。结果表明，hsa-miR-4463、hsa-miR-3945、hsa-miR-548H_4、hsa-miR-920 和 hsa-miR-3652 的变异与胃癌易感性相关。hsa-miR-4463 与 GC 的临床特征（弥漫性胃肿瘤组织学类型、“非贲门”定位区域和发病早）显著相关。我们的研究结果表明，INDELs 可能是胃癌风险的潜在功能性遗传变异。