Centro de Investigación Biomédica, Departamento de Fisiología, Facultad de Medicina, Instituto de Biotecnología, Parque Tecnológico de Ciencias de la Salud, Universidad de Granada, 18016 Granada, Spain.
UGC de Laboratorios Clínicos, Hospital Universitario Clínico San Cecilio, 18016 Granada, Spain.
Int J Mol Sci. 2024 Jun 20;25(12):6784. doi: 10.3390/ijms25126784.
Etiological factors involved in myelodysplastic syndrome (MDS) include immunologic, oxidative stress and inflammatory factors, among others, and these are targets for microRNAs (miRNs). Here, we evaluated whether some miRNs may affect tumor development comparing untreated and 5-azacitidine (5-AZA) MDS-treated patients. Peripheral blood samples were collected from 20 controls and 24 MDS patients, and selected miRNs related to redox balance and inflammation (inflamma-miRs), including miR-18a, miR-21, miR-34a and miR-146a, were isolated and measured by quantitative real-time polymerase chain reaction (qRTPCR). A differential expression profile of miRNs was detected in untreated MDS patients and the 5-AZA group. Inflammation increases miRNs and, specifically, miR-18a, miR-21 and miR-34a were significantly overexpressed in untreated MDS, compared to controls. However, we did not observe any miRN profile alteration during the progression of the disease. On the other hand, 5-AZA treatment tends to restore miRN expression levels. Relating to prognostic risk factors, high-risk MDS groups (high Revised International Prognostic Scoring System (IPSS-R), high cytogenetic risk, high molecular risk (HMR) mutations) tended to be related with higher expression levels of miR-18a and miR-34a. Higher miRN expression is correlated with lower glutathione peroxidase activity, while they are related with a higher profile of pro-inflammatory cytokines (IL-2, IL-6, IL-8, TNF-α). Although our study was limited by the low number of MDS patients included, we identified miRN deregulation involved in MDS development that could regulate redox sensors and inflammatory responses. Finally, 5-AZA treatment is related with lower miRN expression levels in MDS patients.
骨髓增生异常综合征 (MDS) 的病因包括免疫、氧化应激和炎症等因素，这些都是 microRNAs (miRNs) 的作用靶点。在这里，我们评估了一些 miRNs 是否可能通过比较未经治疗和 5-氮杂胞苷 (5-AZA) 治疗的 MDS 患者来影响肿瘤的发展。从 20 名对照者和 24 名 MDS 患者中采集外周血样本，并通过定量实时聚合酶链反应 (qRTPCR) 分离和测量与氧化还原平衡和炎症相关的选定 miRNs (inflamma-miRs)，包括 miR-18a、miR-21、miR-34a 和 miR-146a。在未经治疗的 MDS 患者和 5-AZA 组中检测到 miRNs 的差异表达谱。炎症增加 miRNs，并且与对照组相比，未经治疗的 MDS 中 miR-18a、miR-21 和 miR-34a 的表达明显上调。然而，我们在疾病进展过程中没有观察到任何 miR 谱改变。另一方面，5-AZA 治疗往往会恢复 miR 表达水平。与预后危险因素相关，高风险 MDS 组（高修订国际预后评分系统 (IPSS-R)、高细胞遗传学风险、高分子风险 (HMR) 突变）倾向于与 miR-18a 和 miR-34a 的表达水平升高相关。更高的 miR 表达与谷胱甘肽过氧化物酶活性降低相关，而与促炎细胞因子（IL-2、IL-6、IL-8、TNF-α）的更高谱相关。尽管我们的研究受到纳入的 MDS 患者数量有限的限制，但我们确定了 MDS 发病机制中涉及的 miR 失调，这些失调可能调节氧化还原传感器和炎症反应。最后，5-AZA 治疗与 MDS 患者的 miR 表达水平降低有关。
