Identification of TRNA-derived RNAs in Adipose Tissue from Overweight Type 2 Diabetes Mellitus Patients and Their Potential Biological Functions

Overview

Journal Front Endocrinol (Lausanne)

Specialty Endocrinology

Date 2023 Jul 24

PMID 37484941

Authors

Jie Zhang

Yingfei Xi

Qiuping Fei

Jun Xu

Jinxing Hu

Affiliations

Soon will be listed here.

Abstract

Background: Type 2 diabetes mellitus (T2DM)causes a huge public health burden worldwide, especially for those who are overweight or obese, the pain is often greater. And search for effective targets in overweight T2DM could help improve patient quality of life and prognosis. tRNA-derived RNAs (tsRNAs) are multifunctional regulators that are currently receiving much attention, but there is still a lack of knowledge about tsRNAs in overweight T2DM.

Methods: T2DM patients with BMI ≥ 25 (Overweight group) and BMI< 25 (Control group) were subjected to tsRNA sequencing; differentially expressed tsRNAs in the two groups were analyzed and their expression was verified using qRT-PCR. The biological function of downstream target genes was also evaluated by enrichment analysis.

Results: qRT-PCR evaluation identified a tsRNA with up-regulated expression (tRF-1-28-Glu-TTC-3-M2) and a tsRNA with down-regulated expression (tRF-1-31-His-GTG-1), both of which may be involved in metabolic and energy-related processes.

Conclusion: Dysregulation of tsRNA expression in overweight patients with T2DM suggests a potential role for tsRNA in the development of T2DM.

Citing Articles

Potential Diagnostic Biomarkers of tRNA-Derived Small RNAs in PBMCs for Nonproliferative Diabetic Retinopathy in Patients With Type 2 Diabetes Mellitus.

Ding C, Wang N, Peng A, Wang Z, Li B, Zhang X Transl Vis Sci Technol. 2024; 13(8):32.

PMID: 39167377 PMC: 11343001. DOI: 10.1167/tvst.13.8.32.

References

Wang T, Cao L, He S, Long K, Wang X, Yu H . Small RNA sequencing reveals a novel tsRNA-06018 playing an important role during adipogenic differentiation of hMSCs. J Cell Mol Med. 2020; 24(21):12736-12749. PMC: 7686998. DOI: 10.1111/jcmm.15858. View

Cosentino C, Toivonen S, Diaz Villamil E, Atta M, Ravanat J, Demine S . Pancreatic β-cell tRNA hypomethylation and fragmentation link TRMT10A deficiency with diabetes. Nucleic Acids Res. 2018; 46(19):10302-10318. PMC: 6212784. DOI: 10.1093/nar/gky839. View

Chan P, Lowe T . GtRNAdb: a database of transfer RNA genes detected in genomic sequence. Nucleic Acids Res. 2008; 37(Database issue):D93-7. PMC: 2686519. DOI: 10.1093/nar/gkn787. View

Desjardins E, Steinberg G . Emerging Role of AMPK in Brown and Beige Adipose Tissue (BAT): Implications for Obesity, Insulin Resistance, and Type 2 Diabetes. Curr Diab Rep. 2018; 18(10):80. DOI: 10.1007/s11892-018-1049-6. View

Malone J, Hansen B . Does obesity cause type 2 diabetes mellitus (T2DM)? Or is it the opposite?. Pediatr Diabetes. 2018; 20(1):5-9. DOI: 10.1111/pedi.12787. View

Sarker G, Sun W, Rosenkranz D, Pelczar P, Opitz L, Efthymiou V . Maternal overnutrition programs hedonic and metabolic phenotypes across generations through sperm tsRNAs. Proc Natl Acad Sci U S A. 2019; 116(21):10547-10556. PMC: 6534971. DOI: 10.1073/pnas.1820810116. View

Bjerregaard L, Jensen B, Angquist L, Osler M, Sorensen T, Baker J . Change in Overweight from Childhood to Early Adulthood and Risk of Type 2 Diabetes. N Engl J Med. 2018; 378(14):1302-1312. DOI: 10.1056/NEJMoa1713231. View

Liu B, Cao J, Wang X, Guo C, Liu Y, Wang T . Deciphering the tRNA-derived small RNAs: origin, development, and future. Cell Death Dis. 2021; 13(1):24. PMC: 8692627. DOI: 10.1038/s41419-021-04472-3. View

Li S, Xu Z, Sheng J . tRNA-Derived Small RNA: A Novel Regulatory Small Non-Coding RNA. Genes (Basel). 2018; 9(5). PMC: 5977186. DOI: 10.3390/genes9050246. View

10.

Langmead B . Aligning short sequencing reads with Bowtie. Curr Protoc Bioinformatics. 2010; Chapter 11:Unit 11.7. PMC: 3010897. DOI: 10.1002/0471250953.bi1107s32. View

11.

Xiao L, Wang J, Ju S, Cui M, Jing R . Disorders and roles of tsRNA, snoRNA, snRNA and piRNA in cancer. J Med Genet. 2022; 59(7):623-631. DOI: 10.1136/jmedgenet-2021-108327. View

12.

Khan M, Hashim M, King J, Govender R, Mustafa H, Al Kaabi J . Epidemiology of Type 2 Diabetes - Global Burden of Disease and Forecasted Trends. J Epidemiol Glob Health. 2020; 10(1):107-111. PMC: 7310804. DOI: 10.2991/jegh.k.191028.001. View

13.

Friedlander M, Mackowiak S, Li N, Chen W, Rajewsky N . miRDeep2 accurately identifies known and hundreds of novel microRNA genes in seven animal clades. Nucleic Acids Res. 2011; 40(1):37-52. PMC: 3245920. DOI: 10.1093/nar/gkr688. View

14.

Liu W, Zhou X, Li Y, Zhang S, Cai X, Zhang R . Serum leptin, resistin, and adiponectin levels in obese and non-obese patients with newly diagnosed type 2 diabetes mellitus: A population-based study. Medicine (Baltimore). 2020; 99(6):e19052. PMC: 7015632. DOI: 10.1097/MD.0000000000019052. View

15.

Shen L, Tan Z, Gan M, Li Q, Chen L, Niu L . tRNA-Derived Small Non-Coding RNAs as Novel Epigenetic Molecules Regulating Adipogenesis. Biomolecules. 2019; 9(7). PMC: 6681357. DOI: 10.3390/biom9070274. View

16.

Gupta D, Krueger C, Lastra G . Over-nutrition, obesity and insulin resistance in the development of β-cell dysfunction. Curr Diabetes Rev. 2012; 8(2):76-83. DOI: 10.2174/157339912799424564. View

17.

Robinson M, McCarthy D, Smyth G . edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics. 2009; 26(1):139-40. PMC: 2796818. DOI: 10.1093/bioinformatics/btp616. View

18.

Pillon N, Loos R, Marshall S, Zierath J . Metabolic consequences of obesity and type 2 diabetes: Balancing genes and environment for personalized care. Cell. 2021; 184(6):1530-1544. PMC: 9191863. DOI: 10.1016/j.cell.2021.02.012. View

19.

Zhang X, Mao Z, Jin X, Wang Y, Dong Y, Zhang C . Identification of a tsRNA Contributor to Impaired Diabetic Wound Healing via High Glucose-Induced Endothelial Dysfunction. Diabetes Metab Syndr Obes. 2023; 16:285-298. PMC: 9899021. DOI: 10.2147/DMSO.S379473. View

20.

Wing R, Lang W, Wadden T, Safford M, Knowler W, Bertoni A . Benefits of modest weight loss in improving cardiovascular risk factors in overweight and obese individuals with type 2 diabetes. Diabetes Care. 2011; 34(7):1481-6. PMC: 3120182. DOI: 10.2337/dc10-2415. View