Can miR-145-5p be used as a marker in diabetic patients?

Shahrokhi, Seyedeh Zahra; Saeidi, Leyla; Sadatamini, Mirsaber; Jafarzadeh, Meisam; Rahimipour, Ali; Kazerouni, Faranak

doi:10.1080/13813455.2020.1762657

Cited by 24 publications

(19 citation statements)

References 26 publications

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“…The RAET1E-AS1 -miR-145-5p -WNT11/BMPER axis was selected and conformed based on the ceRNA relationship and expressional correlation analyses. MiR-145-5p have been recognized as a tumor repressor in many kinds of cancers [60,61], a suppressor in osteogenic differentiation of ASCs [62], and a biomarker for the diagnosis of type two diabetes because of the low level in diabetic plasma [63]. Our study found overexpression of miR-145-5p in O-ASCs could promote their proliferation and migration and rejuvenate their senescent phenotype, which was contrary to their behavior in cancer cells.…”

Section: Discussionmentioning

confidence: 61%

The whole profiling and competing endogenous RNA network analyses of noncoding RNAs in adipose stem cells from diabetic, old and young patients

Ren

Xiong

Chen

et al. 2021

Preprint

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BackgroundMesenchymal stem cells including adipose stem cells (ASCs) have a huge potential in the field of translational medicine. Unfortunately, multiple factors including older age, co-existing diabetes and obesity may impair cellular function, which hinders the overall effectiveness of autologous stem cell therapy. Noncoding RNAs including microRNAs (miRNA), long ncRNAs (lncRNAs), and circular RNAs (circRNAs) have been demonstrated to play an important role in stem cell biology. However, the whole expression pattern and interaction of these RNAs in ASCs related to diabetes and aging remain unknown.MethodEdU, transwell and β-galactosidase staining assays were performed to assess the proliferation, migration and senescence of ASCs isolated from diabetic (D-ASCs), old (O-ASCs), and young (Y-ASCs) donators. The abilities of these ASCs modulating endothelial cells and fibroblasts functions were evaluated by tube formation and wound scratch assays. We conducted high-throughput RNA sequencing (RNA-seq) in these ASCs to uncover the differentially expressed (DE) RNAs. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and protein-protein interactions (PPI) analyses were performed to interpret the mRNAs with significant differences. The lncRNAs or circRNAs associated competing endogenous RNA (ceRNA) networks were constructed based on the bioinformatic analyses and real-time polymerase chain reaction (RT-PCR) results. The miR-145-5p mimics were transfected into old ASCs and verified by PCR.ResultsASCs from diabetic and old donators showed inferior migration ability and increased cellular senescence. Besides, old ASCs have decreased capacities for promoting endothelial cells angiogenesis and fibroblasts migration comparing to young ASCs. The DE miRNAs, mRNAs, lncRNAs and circRNAs were successfully identified by RNA-seq in O-ASCs vs Y-ASCs and D-ASCs vs O-ASCs. GO and KEGG analyses demonstrated DE mRNAs were significantly enriched in aging and cell senescence terms separately. PPI networks performed critical DE mRNAs in above groups. MiRNAs with high fold change and low p value were validated by PCR. The four ceRNA networks were conducted based on the bioinformatic analyses and validated miRNAs. The selected mRNAs, lncRNAs and circRNAs in PPI and ceRNA networks were further evaluated by PCR. Then, the ceRNA subnetworks were constructed based on above validated RNAs. In addition, the lncRNA RAET1E-AS1 - miR-145-5p - WNT11/BMPER axis was selected and validated by the PCR and correlation analyses. Finally, overexpression of miR-145-5p could rejuvenate old ASCs phenotype and augment their abilities for modulating endothelial cells and fibroblasts functions.ConclusionTaken together, our research may provide new clues to unveil the underlying mechanisms of ASCs dysfunction, and disclose novel targets for restoring their therapeutic properties.

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Section: Discussionmentioning

confidence: 61%

The whole profiling and competing endogenous RNA network analyses of noncoding RNAs in adipose stem cells from diabetic, old and young patients

Ren

Xiong

Chen

et al. 2021

Preprint

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“… 30 The expression level of miR‐145‐5p is significantly downregulated in T2DM, which may be a potential diagnostic biomarker for T2DM. 31 These studies have further demonstrated that miR‐145 may have an important regulatory role in the progression of diabetes and also suggest that hsa_circ_0115355 may regulate the progression of diabetes through miR‐145.…”

Section: Discussionmentioning

confidence: 93%

hsa_circ_0115355 promotes pancreatic β‐cell function in patients with type 2 diabetes through the miR‐145/SIRT1 axis

Dai

Zhang

et al. 2022

Clinical Laboratory Analysis

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Background: Type 2 diabetes mellitus (T2DM) is a complex metabolic disease closely related to obesity, a growing global health problem. T2DM is characterized by decreased islet beta-cell mass and impaired insulin release from these cells, and this dysfunction is exacerbated by hyperglycemia (glucolipotoxicity). Circular RNAs (circR-NAs) are abnormally expressed and play a regulatory role in T2DM.Objective: This study aimed to evaluate the function and molecular mechanism of hsa_circ_0115355 in the progression of T2DM. Methods: The regulatory effect of hsa_circ_0115355 on INS-1 cell function was assessed under glucolipotoxicity by MTT, flow cytometry analysis, and insulin secretion assay. Dual-luciferase experiments revealed a direct interaction of hsa_circ_0115355 with miR-145 and miR-145 with SIRT1. Furthermore, the regulatory role of the hsa_ circ_0115355/miR-145/SIRT1 axis was verified by examining the function of INS-1.Results: In this study, hsa_circ_0115355 was significantly underexpressed in both patients with T2DM and INS-1 cell lines. This study thus showed that hsa_circ_0115355 inhibits the occurrence and development of T2DM by regulating the expression of SIRT1 by adsorbing miR-145. Conclusion:The underexpression hsa_circ_0115355 is also a potential novel diagnostic marker and therapeutic target for T2DM.

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“…Even though it has not been verified whether gain and loss of function of miR-145 in adipose tissue affect lipolysis and adiposity in vivo, in humans, obesity is associated with its increased expression in SAT, while NAFLD is also associated with its increased expression in VAT [ 34 , 37 , 53 ]. However, it should be mentioned that the 5p isoform (miR-145-5p) was found to be downregulated in the SAT of morbidly obese individuals, while its serum concentrations are decreased in the course of T2DM and prediabetes [ 30 , 115 ].…”

Section: Microrna In the Regulation Of Adipose Tissue Functionmentioning

confidence: 99%

“…In turn, a low circulating miR-155 level may suggest a need for regular control of the lipid profile [ 93 ]. On the contrary, high miR-145-5p and miR-199a-5p serum concentrations seem to be a marker of metabolic health [ 8 , 115 ]. Blood levels of some other miRNAs (e.g., miR-425) can also act as predictors of successful lifestyle interventions in obese diabetic patients [ 110 ].…”

Section: Final Remarks and Conclusionmentioning

confidence: 99%

microRNAs in Human Adipose Tissue Physiology and Dysfunction

Kuryłowicz

2021

Cells

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In recent years, there has been a large amount of evidence on the role of microRNA (miRNA) in regulating adipose tissue physiology. Indeed, miRNAs control critical steps in adipocyte differentiation, proliferation and browning, as well as lipolysis, lipogenesis and adipokine secretion. Overnutrition leads to a significant change in the adipocyte miRNOME, resulting in adipose tissue dysfunction. Moreover, via secreted mediators, dysfunctional adipocytes may impair the function of other organs and tissues. However, given their potential to control cell and whole-body energy expenditure, miRNAs also represent critical therapeutic targets for treating obesity and related metabolic complications. This review attempts to integrate present concepts on the role miRNAs play in adipose tissue physiology and obesity-related dysfunction and data from pre-clinical and clinical studies on the diagnostic or therapeutic potential of miRNA in obesity and its related complications.

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Can miR-145-5p be used as a marker in diabetic patients?

Cited by 24 publications

References 26 publications

The whole profiling and competing endogenous RNA network analyses of noncoding RNAs in adipose stem cells from diabetic, old and young patients

The whole profiling and competing endogenous RNA network analyses of noncoding RNAs in adipose stem cells from diabetic, old and young patients

hsa_circ_0115355 promotes pancreatic β‐cell function in patients with type 2 diabetes through the miR‐145/SIRT1 axis

microRNAs in Human Adipose Tissue Physiology and Dysfunction

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