Molecular Biology and Genomics Department, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, JAL, Mexico.
Immunology Research Laboratory, Immunology Division, Programa Internacional de Medicina, Universidad Autónoma de Guadalajara, Guadalajara, JAL, Mexico.
J Immunol Res. 2018 Mar 29;2018:2474529. doi: 10.1155/2018/2474529. eCollection 2018.
Rheumatoid arthritis (RA) is a systemic autoimmune disease with severe joint inflammation and destruction associated with an inflammatory environment. The etiology behind RA remains to be elucidated; most updated concepts include the participation of environmental, proteomic, epigenetic, and genetic factors. Epigenetic is considered the missing link to explain genetic diversification among RA patients. Within epigenetic factors participating in RA, miRNAs are defined as small noncoding molecules with a length of approximately 22 nucleotides, capable of gene expression modulation, either negatively through inhibition of translation and degradation of the mRNA or positively through increasing the translation rate. Over the last decade and due to the feasibility of the identification of miRNAs among different tissues and compartments, they have been proposed as biomarkers for diagnosis, prognosis, and response to treatment in different pathologies. Nevertheless, miRNAs seem to be important regulators of networks instead of single genes; their hypothetical use as biomarkers needs to rely on a functional integrative description of their effects in the biological process of autoimmune conditions which until now is missing. Therefore, we underwent a bibliographic search for review and original articles related to miRNAs and their possible implications in rheumatoid arthritis. We found 48 different studies using the key words "miRNAs" or "micro-RNAs" and "rheumatoid arthritis" with restriction of publication dates from 2011 to 2016, in humans, using the English language. After a critical reading, we provide in this paper a functional view with respect to miRNA biogenesis, interaction with targets that are expressed in specific cells and tissues, during different stages of inflammatory responses associated with RA, and recognized specific areas where miRNAs might also have a pathogenic role but remain undescribed. Our results will be useful in designing future research projects that can support miRNAs as biomarkers or therapeutic targets in RA.
类风湿关节炎（RA）是一种系统性自身免疫性疾病，伴有严重的关节炎症和破坏，并与炎症环境有关。RA 的病因仍不清楚；最新的概念包括环境、蛋白质组学、表观遗传学和遗传因素的参与。表观遗传学被认为是解释 RA 患者遗传多样性的缺失环节。在参与 RA 的表观遗传因素中，miRNAs 被定义为大约 22 个核苷酸长度的小非编码分子，能够调节基因表达，要么通过抑制翻译和降解 mRNA 来负调控，要么通过增加翻译速率来正调控。在过去的十年中，由于在不同组织和隔室中鉴定 miRNAs 的可行性，它们已被提议作为不同疾病的诊断、预后和治疗反应的生物标志物。然而，miRNAs 似乎是网络而不是单个基因的重要调节剂；它们作为生物标志物的假设用途需要依赖于对它们在自身免疫疾病的生物学过程中的作用的功能综合描述，而到目前为止这一描述还不存在。因此，我们进行了文献检索，以综述和原始文章为基础，研究 miRNAs 及其在类风湿关节炎中的可能影响。我们使用关键词“miRNAs”或“micro-RNAs”和“rheumatoid arthritis”，并限制了发表日期为 2011 年至 2016 年，在人类中，使用英语，检索到了 48 项不同的研究。经过批判性阅读，我们在本文中提供了一个关于 miRNA 生物发生、与在特定细胞和组织中表达的靶标相互作用的功能观点，这些靶标在与 RA 相关的炎症反应的不同阶段，以及公认的 miRNA 可能具有致病性作用但尚未描述的特定区域。我们的研究结果将有助于设计未来的研究项目，这些项目可以支持 miRNA 作为 RA 的生物标志物或治疗靶点。
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