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*Re-Print: The NS-3 Mixture of δ-Tocotrienol, Vitamin D3 and Resveratrol Modulates Gene Expression of Several Novel MicroRNAs Identified by Transcriptomic Analyses in People with Type 2 Diabetes

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Re-print: Research | DOI: https://doi.org/10.31579/2768-2757/118

*Re-Print: The NS-3 Mixture of δ-Tocotrienol, Vitamin D3 and Resveratrol Modulates Gene Expression of Several Novel MicroRNAs Identified by Transcriptomic Analyses in People with Type 2 Diabetes

  • Asaf A Qureshi 1**

1 Department of Biomedical Science, School of Medicine, University of Missouri-Kansas City, 2411 Holmes Street, Kansas City, MO 64108, USA.

2 Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology (AFIP), National University of Medical Sciences, Rawalpindi, 64000, Pakistan.

3 Pharmacology/Toxicology, School of Pharmacy, University of Missouri-Kansas City, 2464 Charlotte Street, Kansas City, MO 64108, USA.

4 Mayo Clinic, 200 First Street SW, Rochester, Minnesota, 55905, USA. 

5 Division of Experimental and Translational Genetics, Department of Pediatrics, Children’s Mercy Hospital, 2401 Gillham Road, Kansas City, MO. 64108, USA.

*Corresponding Author: Asaf A. Qureshi, Ph.D. Department of Biomedical Science, 2411 Holmes Street, School of Medicine, University of Missouri, Kansas City, MO 64108, USA. E-mail: qureshia@umsystem.edu

Citation: Asaf A Qureshi, Dilshad A. Khan, Wajiha Mahjabeen, Nilofer Qureshia, Mrunal K. Dehankar, (2024), *Re-Print: The NS-3 Mixture of δ-Tocotrienol, Vitamin D3 and Resveratrol Modulates Gene Expression of Several Novel MicroRNAs Identified by Transcriptomic Analyses in People with Type 2 Diabetes, Journal of Clinical Surgery and Research, 5(3); DOI:10.31579/2768-2757/118

Copyright: © 2024, Asaf A. Qureshi. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Received: 14 March 2024 | Accepted: 22 March 2024 | Published: 04 April 2024

Keywords: T2DM; δ-tocotrienol; vitamin D3; resveratrol; miRNA-29b-3p; mRNA-AL1621513

Abstract

Aims: Type 2 diabetes mellitus is due to hyperglycemia, therefore fasting glucose and glycosylated hemoglobin (HbA1c) levels are used as biomarkers to determine onset of diabetes.  RT-PCR estimation of pooled total mRNAs of EDTA treated whole blood (plasma) obtained after the treatment of NS-3 mixture of d-tocotrienol, vitamin D3, resveratrol of people with type 2 diabetes mellitus (T2DM) for 24 weeks, showed significant down-regulation of gene expression of several diabetes biomarkers (IRS-1, SOD-2, GCKR, IGFBP-2) and cytokines (IL-4, IL-6) as compared to pre-treatment values. Present study investigates the effectiveness of NS-3 on gene expression of mRNAs, miRNAs, and paired mRNA-miRNA in people with T2DM.

Methods: Present study is an extension of a randomized placebo controlled double-blinded clinical trial of T2DM (n = 56/group) given two capsules/d of cellulose/olive oil (placebo), or NS-3 for 24-weeks. Pure mRNAs and miRNAs of plasma of pre-dose versus post-dose of NS-3 treated samples were analyzed by next generation sequencing (NGS). Data was uploaded into “Ingenuity Pathways Analyses”.

Results: A total of 4000 genes are considered significant, based on > 2-fold gene expression changes. Out of which 1373 genes are significantly differentially expressed in pre-dose vs post-dose (P < 0.02) samples, 20 are up-regulated and 27 are down-regulated of NS-3 treated RNAs of T2DM. Gene expression of up-regulated miR-29b-3p modulates (GLUT4, insulin resistance), miR-624-5p (nephropathy biomarker), miR-361-5p (chronic inflammation), miR-130a-3p (glucose metabolism, insulin secretion), miR-3912-3p (lipid metabolism), and miR-11401 (cellular transcription). The miR-374c-5p (insulin resistance), miR-4326 (HbA1c level)), miR-874-3p (b-cell function) are down-regulated of NS-3 treated people with T2DM. Whereas messengerR-ML-1621513 (oxidative/stress), mR-CTD-2349P217 (insulin-mediated glucose-uptake), are up-regulated, and mR-CTC-246B1810 (b-cell/biology) are down-regulated in T2DM after NS-3 treatment. Venn diagrams have established genetic regulatory network images and canonical signaling pathways for mRNA, miRNA, and paired mRNA-miRNA of gene expression profiles of pre-dose vs post-dose of NS-3 treatment group.

Conclusions: The NS-3 treatment of people with T2DM indicates up- or down-regulation of several new miRNAs (miR-29b-3p, miR-624-5p, miR-361-5p, miR-130a-3p, miR-3912-3p,  miR-374c-5p, miR-4326 [HbA1c], miR-1247-3p, miR-874-5p) which may be used to identify onset of T2DM. Overexpression of mRNA-AL1621513 indicates oxidative stress in people with T2DM, resulting in complications of diabetes (neuropathy, retinopathy, and stroke).

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