Ruknarong Laongthip, Boonthongkaew Chongchira, Chuangchot Nisa, Jumnainsong Amonrat, Leelayuwat Naruemon, Jusakul Apinya, Gaudieri Silvana, Leelayuwat Chanvit
Centre for Research and Development of Medical Diagnostic Laboratories (CMDL), Faculty of Associated Medical Sciences, Khon Kaen University, Khon kean, Thailand.
Biomedical Sciences Program, Graduate School, Khon Kaen University, Khon Kaen, Thailand.
PeerJ. 2021 Feb 4;9:e10776. doi: 10.7717/peerj.10776. eCollection 2021.
Vitamin C is an essential element required for normal metabolic function. We investigated the effect of vitamin C supplementation on circulating miRNA (miR) expression in subjects with poorly controlled type 2 diabetes mellitus (T2DM). Changes in miR expression were also correlated with clinical measures of disease.
Pre- and post-vitamin C supplementation samples from five participants who had increased vitamin C levels, improved oxidative status and polymorphonuclear (PMN) function after receiving 1,000 mg of vitamin C daily for six weeks were screened for miRNA expression using the NanoString miRNA assay. Differences in miRNA expression identified from the miRNA screen were validated by qRT-PCR.
Four miRNAs showed significantly different expression post-vitamin C supplementation relative to baseline, including the down-regulation of miR-451a (-1.72 fold change (FC), = 0.036) and up-regulation of miR-1253 (0.62 FC, = 0.027), miR-1290 (0.53 FC, = 0.036) and miR-644a (0.5 FC, = 0.042). The validation study showed only miR-451a expression was significantly different from baseline with vitamin C supplementation. MiR-451a expression was negatively correlated with vitamin C levels ( = - 0.497, = 0.049) but positively correlated with levels of malondialdehyde (MDA) ( = 0.584, = 0.017), cholesterol ( = 0.564, = 0.022) and low-density lipoproteins (LDL) ( = 0.522, = 0.037). Bioinformatics analysis of the putative target genes of miR-451a indicated gene functions related to signaling pathways involved in cellular processes, such as the mammalian target of rapamycin (mTOR) signaling pathway.
Vitamin C supplementation altered circulating miR-451a expression. The results from this pilot study suggest that miRNAs could be used as biomarkers to indicate oxidative status in subjects with T2DM and with poor glycemic control and could lead to a novel molecular strategy to reduce oxidative stress in T2DM.
维生素C是正常代谢功能所需的必需元素。我们研究了补充维生素C对2型糖尿病（T2DM）控制不佳患者循环miRNA（miR）表达的影响。miR表达的变化也与疾病的临床指标相关。
对五名参与者补充维生素C前后的样本进行检测，这五名参与者在每天服用1000毫克维生素C，持续六周后，维生素C水平升高，氧化状态和多形核白细胞（PMN）功能得到改善。使用NanoString miRNA检测法筛选miRNA表达。通过qRT-PCR验证从miRNA筛选中鉴定出的miRNA表达差异。
四种miRNA在补充维生素C后相对于基线显示出显著不同的表达，包括miR-451a的下调（-1.72倍变化（FC），P = 0.036）以及miR-1253（0.62 FC，P = 0.027）、miR-1290（0.53 FC，P = 0.036）和miR-644a（0.5 FC，P = 0.042）的上调。验证研究表明，补充维生素C后只有miR-451a的表达与基线有显著差异。miR-451a的表达与维生素C水平呈负相关（r = - 0.497，P = 0.049），但与丙二醛（MDA）水平呈正相关（r = 0.584，P = 0.017）、胆固醇（r = 0.564，P = 0.022）和低密度脂蛋白（LDL）（r = 0.522，P = 0.037）。对miR-451a的假定靶基因进行生物信息学分析表明，其基因功能与细胞过程中涉及的信号通路有关，如雷帕霉素靶蛋白（mTOR）信号通路。
补充维生素C改变了循环miR-451a的表达。这项初步研究的结果表明，miRNA可作为生物标志物来指示T2DM且血糖控制不佳患者的氧化状态，并可能导致一种减少T2DM氧化应激的新分子策略。
