Abstract
Editor-in-Chief
Ramzi Ajjan
Leeds University, UK
Dear Editor in chief
We read the article with great interest recently published by Ma et al. Early diagnosis value of lncRNA SNHG14 combined with miR-493-5p in gestational diabetes mellitus and its correlation with pregnancy outcome 1 in Diabetes and Vascular Disease Research, which explores the diagnostic value of lncRNA, SNHG14, and miR-493-5p in Gestational diabetes (GDM). The identification of early indicators in GDM is timely and clinically relevant. As medical students interested in pathophysiology and public health, we found this study quite appealing. The study not only expands on existing information, but it also opens up new avenues for future research. The authors’ ability to turn complicated facts into relevant ideas is quite commendable. Their study provides a comprehensive understanding of different biomarkers that can be used as a diagnostic tool for the early detection of GDM, along with different main key factors that influence the prevalence of GDM. The evidence presented is crucial, and it will likely assist shaping local health strategies. However, we would like to point out a few things to consider
A prominent yet largely ignored area in current research literature is the effect of ethnicity on the expression and diagnostic potential of lncRNA SNHG14 and miR-493-5p in gestational diabetes mellitus (GDM). While there is evidence that ethnicity plays a role in the expression of miRNA. Re-analysis of the expression of GDM-related miRNAs, miR-155 and mmiR-137, indicated differences in the expression between Turkish and Chinese populations. 2 Recent reviews identify race and ethnicity as important influence on the expression of placental non-coding RNAs in GDM. 3 While SNHG14 has previously been implicated in complications of diabetes, such as diabetic kidney disease in Asian cohorts, 4 the clinical value of miR-493-5p to diagnose GDM, or the expression of these markers in relation to GDM was not substantiated in the literature. Importantly, there is growing evidence to support the potential of circulating microRNAs as diagnostic tools in GDM to test these markers in underrepresented populations, such as Middle Eastern cohorts. 2 This gap validates a need for ethnicity and future studies to examine multi-ethnic cohorts to determine whether these biomarkers are a reliable predictive tool across racial groups. These outcomes are vital for developing equitable, population-specific screening tools and advancing personalized medicine in GDM.
Moreover, we would wish to propose humbly that the natural occurrence of 293T/HEK293 cells selection in the luciferase-reporter assay is not perhaps the most physiologically relevant model, at least when seeking to study non-coding RNA activity in the context of gestational diabetes mellitus (GDM), SNHG14 and miR-493-5p being cited as examples. As postulated in recent works, the main source of the pathophysiology of GDM is the placenta which secretes the placental hormones that cause insulin resistance in late pregnancy. 5 Additionally, there is evidence that such miRNAs like miR-493-5p actively gets secreted from the placenta in exosomes and actually exert an influence on maternal metabolic regulation. 6 Also, the expression of placental genes such as the regulation of long non-coding RNAs and miRNAs is a highly specific and dynamically correlated with maternal and fetal outcomes. 7 Considering these understandings, a placental derived cellular or trophoblast- based model type will provide a more context relevant platform to examine the SNHG14 and miR-493-5p in GDM.
Additionally, there is a serious methodological concern about using GAPDH as a reference gene for miRNA quantification by the authors. Semi-random control GAPDH, an mRNA transcript, is not an effective normalization target of miRNA due to mere differences in transcriptional regulation, stability, and molecular processing. Normalization of efficient miRNA quantification is essential, particularly in clinical samples such as plasma or serum, where RNA yields are insufficient and experimental variation is high. Experimental data show that commonly used reference genes like GAPDH and U6 show uneven expression, while particular miRNAs (e.g., miR-191, miR-103) show more stability across multiple tissue types and experimental settings. 8 In addition a control that is not miRNA specific could introduce high levels of bias in data interpretation, making it imperative to employ miRNA-specific modes of normalization or spike-in controls in qRT-PCR procedures. 9
Nonetheless, the study still offers a solid base of understanding the investigation of diagnostic tools to lead to early detection of Gestational diabetes that can lead to great changes in patient care.
