Division of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Kunming, 650032, China.
Transfusion Medicine Research Department, Yunnan Kunming Blood Center, Kunming, 650500, China.
Clinics (Sao Paulo). 2021 Sep 3;76:e2502. doi: 10.6061/clinics/2021/e2502. eCollection 2021.
Diagnosis and management of essential hypertension (EH) or type 2 diabetes mellitus (T2DM) by combining comprehensive treatment and classificatory diagnosis have been continuously improved. However, understanding the pathogenesis of EH patients with concomitant T2DM and subsequent treatment remain the major challenges owing to the lack of non-invasive biomarkers and information regarding the underlying mechanisms.
Herein, we collected 200 serum samples from EH and/or T2DM patients and healthy donors (N). Gene-expression profiling was conducted to identify candidate microRNAs with clinical significance. Then, a larger cohort of the aforementioned patients and 50 N were used to identify the correlation between the tumor suppressor miR-195-5p and EH and/or T2DM. The dual-luciferase reporter assay was used to explore the target genes of miR-195-5p. The suppressive effects of miR-195-5p on the 3'-UTR of the dopamine receptor D1 (DRD1) transcript in EH patients with concomitant T2DM were verified as well.
Compared with that in other groups, serum miR-195-5p was highly downregulated in EH patients with concomitant T2DM. miR-195-5p overexpression efficiently suppressed DRD1 expression by binding to the two 3'-UTRs. Additionally, two single nucleotide polymorphisms, including 231T-A and 233C-G, in the miR-195-5p binding sites of the DRD1 3'-UTR were further identified. Collectively, we identified the potential clinical significance of DRD1 regulation by miR-195-5p in EH patients with concomitant T2DM.
Our data suggested that miR-195-5p circulating in the peripheral blood served as a novel biomarker and therapeutic target for EH and T2DM, which could eventually help address major challenges during the diagnosis and treatment of EH and T2DM.
通过综合治疗和分类诊断,不断提高原发性高血压(EH)或 2 型糖尿病(T2DM)的诊断和治疗水平。然而,由于缺乏非侵入性生物标志物和EH 患者伴发 T2DM 潜在机制的相关信息,EH 患者伴发 T2DM 的发病机制及其后续治疗仍然是主要挑战。
本研究收集了 200 例 EH 和/或 T2DM 患者及健康对照者(N)的血清样本,进行基因表达谱分析,以确定具有临床意义的候选 microRNA。然后,使用更大的患者队列和 50 名 N 来确定肿瘤抑制因子 miR-195-5p 与 EH 和/或 T2DM 的相关性。双荧光素酶报告基因检测用于探索 miR-195-5p 的靶基因。还验证了 miR-195-5p 在 EH 伴发 T2DM 患者中对多巴胺受体 D1(DRD1)转录物 3'-UTR 的抑制作用。
与其他组相比,EH 伴发 T2DM 患者的血清 miR-195-5p 水平显著下调。miR-195-5p 通过结合两个 3'-UTRs 有效地抑制了 DRD1 的表达。此外,还进一步鉴定了 DRD1 3'-UTR 中 miR-195-5p 结合位点的两个单核苷酸多态性,包括 231T-A 和 233C-G。总之,我们鉴定了 miR-195-5p 对 EH 伴发 T2DM 患者中 DRD1 调节的潜在临床意义。
我们的数据表明,外周血循环中的 miR-195-5p 可作为 EH 和 T2DM 的新型生物标志物和治疗靶点,最终有助于解决 EH 和 T2DM 诊断和治疗中的主要挑战。