Understanding the lncRNA/miRNA-NFκB regulatory network in diabetes mellitus: From function to clinical translation

Hoorzad, Parisa; Mousavinasab, Fatemehsadat; Tofigh, Pouya; Kalahroud, Elham Mazaheri; Aghaei-Zarch, Seyed Mohsen; Salehi, Ali; Fattahi, Mehdi; Le, Binh Nguyen

doi:10.1016/j.diabres.2023.110804

Cited by 10 publications

(4 citation statements)

References 106 publications

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“…In breast cancer, it is the dominant regulator in metabolizing glucose hence able to promote the energy metabolism through few pathways. Moreover, the coordination between NF-κB-miR-155 axis and NF-κB-miR-146a axis may also upregulating the inflammatory reaction ( Hoorzad et al, 2023 ). The above founding all indicate high level of miR-155 is potent as a role that inhibiting the activity of immune response.…”

Section: Mirna and Cancer Immune Evasionmentioning

confidence: 99%

Mapping the function of MicroRNAs as a critical regulator of tumor-immune cell communication in breast cancer and potential treatment strategies

Abdul Manap,

Wisham,

Wong

et al. 2024

Front. Cell Dev. Biol.

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Among women, breast cancer ranks as the most prevalent form of cancer, and the presence of metastases significantly reduces prognosis and diminishes overall survival rates. Gaining insights into the biological mechanisms governing the conversion of cancer cells, their subsequent spread to other areas of the body, and the immune system’s monitoring of tumor growth will contribute to the advancement of more efficient and targeted therapies. MicroRNAs (miRNAs) play a critical role in the interaction between tumor cells and immune cells, facilitating tumor cells’ evasion of the immune system and promoting cancer progression. Additionally, miRNAs also influence metastasis formation, including the establishment of metastatic sites and the transformation of tumor cells into migratory phenotypes. Specifically, dysregulated expression of these genes has been associated with abnormal expression of oncogenes and tumor suppressor genes, thereby facilitating tumor development. This study aims to provide a concise overview of the significance and function of miRNAs in breast cancer, focusing on their involvement as tumor suppressors in the antitumor immune response and as oncogenes in metastasis formation. Furthermore, miRNAs hold tremendous potential as targets for gene therapy due to their ability to modulate specific pathways that can either promote or suppress carcinogenesis. This perspective highlights the latest strategies developed for miRNA-based therapies.

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Section: Mirna and Cancer Immune Evasionmentioning

confidence: 99%

Mapping the function of MicroRNAs as a critical regulator of tumor-immune cell communication in breast cancer and potential treatment strategies

Abdul Manap,

Wisham,

Wong

et al. 2024

Front. Cell Dev. Biol.

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“…The critical role of NF-κB signaling in the emergence of metabolic disorders has been well studied. NF-κB is an important regulator of many inflammatory chemokines and cytokines in a variety of metabolic tissues ( 65 ). The NF-κB signaling pathway is an important inflammatory pathway, and many MicroRNAs are involved in the signaling process of the NF-κB pathway ( Figure 2 , Table 2 ).…”

Section: Microrna Intensification Of Diabetic Retinal Neurodegenerati...mentioning

confidence: 99%

Role of MicroRNA in linking diabetic retinal neurodegeneration and vascular degeneration

Zhao,

Cai,

Pan

et al. 2024

Front. Endocrinol.

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Diabetic retinopathy is the major cause of blindness in diabetic patients, with limited treatment options that do not always restore optimal vision. Retinal nerve degeneration and vascular degeneration are two primary pathological processes of diabetic retinopathy. The retinal nervous system and vascular cells have a close coupling relationship. The connection between neurodegeneration and vascular degeneration is not yet fully understood. Recent studies have found that microRNA plays a role in regulating diabetic retinal neurovascular degeneration and can help delay the progression of the disease. This article will review how microRNA acts as a bridge connecting diabetic retinal neurodegeneration and vascular degeneration, focusing on the mechanisms of apoptosis, oxidative stress, inflammation, and endothelial factors. The aim is to identify valuable targets for new research and clinical treatment of diabetic retinopathy.

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“…In endothelial cells, induction Frontiers in Pharmacology frontiersin.org of NF-κB results in overexpression of vascular cell adhesion molecule-1 (VCAM-1) and thus increased adhesion of inflammatory cells to the vascular endothelium. This NF-κBinduced proliferation and inflammation results in vascular remodeling and chronic vascular invasion (Choi, 2023;Hoorzad et al, 2023). The main poze of verapamil showed three polar contacts with NF-κB through SER-220, SER-226, and deoxyadenosine (DA)-509.…”

Section: Molecular Docking Analysismentioning

confidence: 99%

Preliminary evaluation of the antiglycoxidant activity of verapamil using various in vitro and in silico biochemical/biophysical methods

Nesterowicz,

Lauko,

Dańkowska

et al. 2023

Front. Pharmacol.

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Introduction: Glycoxidative stress is essential for linking glucose disturbances and cardiovascular diseases. Unfortunately, contemporary antidiabetic drugs do not have an antiglycative effect but only lower blood glucose levels. Therefore, there is an intense search for substances that could inhibit protein glycation and prevent diabetic complications. A potential antioxidant activity has been demonstrated with verapamil, a phenylalkylamine derivative belonging to selective calcium channel blockers. Verapamil has a well-established position in cardiology due to its wide range of indications and good safety profile. Nevertheless, the antidiabetic activity of verapamil is still unclear. We are the first to comprehensively evaluate the verapamil’s effect on protein glycoxidation using various in vitro and in silico models.Methods: Bovine serum albumin (BSA) was used to assess the rate of glycoxidation inhibition by verapamil. As glycating factors, sugars (glucose, fructose, and ribose) and aldehyde (glyoxal) were used. Chloramine T was used as an oxidizing agent. Aminoguanidine (protein glycation inhibitor) and Trolox (antioxidant) were used as control substances. The biomarkers of oxidation (total thiols, protein carbonyls, advanced oxidation protein products), glycation (Amadori products, β-amyloid, advanced glycation end products [AGEs]), and glycoxidation (tryptophan, kynurenine, N-formylkynurenine, dityrosine) were evaluated using colorimetric and fluorimetric methods. The mechanism of antiglycative activity of verapamil was assessed using in silico docking to study its interaction with BSA, glycosidases, and seventeen AGE pathway proteins.Results: In all in vitro models, biomarkers of protein glycation, oxidation, and glycoxidation were significantly ameliorated under the influence of verapamil. The glycoxidation inhibition rate by verapamil is comparable to that of potent antiglycating agents and antioxidants. The molecular docking simulations showed that verapamil bound preferentially to amino acids prone to glycoxidative damage out of an α-glucosidase’s active center. Among all AGE pathway proteins, verapamil was best docked with the Janus kinase 2 (JAK2) and nuclear factor-κB (NF-κB).Discussion: The results of our study confirm the antiglycoxidant properties of verapamil. The drug’s action is comparable to recognized substances protecting against oxidative and glycation modifications. Verapamil may be particularly helpful in patients with cardiovascular disease and concomitant diabetes. Studies in animal models and humans are needed to confirm verapamil’s antiglycative/antidiabetic activity.

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Understanding the lncRNA/miRNA-NFκB regulatory network in diabetes mellitus: From function to clinical translation

Cited by 10 publications

References 106 publications

Mapping the function of MicroRNAs as a critical regulator of tumor-immune cell communication in breast cancer and potential treatment strategies

Mapping the function of MicroRNAs as a critical regulator of tumor-immune cell communication in breast cancer and potential treatment strategies

Role of MicroRNA in linking diabetic retinal neurodegeneration and vascular degeneration

Preliminary evaluation of the antiglycoxidant activity of verapamil using various in vitro and in silico biochemical/biophysical methods

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