Crosstalk Between microRNAs and the Pathological Features of Secondary Lymphedema

Yusof, Khairunnisa’ Md; Groen, Kira; Rosli, Rozita; Avery‐Kiejda, Kelly A.

doi:10.3389/fcell.2021.732415

Cited by 5 publications

(3 citation statements)

References 119 publications

(156 reference statements)

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“…P. gingivalis LPS induces the overexpression of miRNAs 146-a and -b in gingival fibroblasts, subsequently enhancing the secretion of TNF-α, IL-6, and IL-1β. [ 43 , 44 , 45 ] Furthermore, miRNA-155 promotes the formation of atherosclerotic plaques, and its downregulation following NSPT may offer benefits in reducing CVD risk in PD and DM patients. [ 22 , 40 ]…”

Section: Discussionmentioning

confidence: 99%

Role of microRNAs in Diabetes-Associated Periodontitis: A Scoping Review

Agnihotri,

Gaur,

Bhat

2024

J Int Soc Prev Community Dent

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Aim: Diabetes mellitus (DM), a metabolic disorder, exhibits a bidirectional relationship with periodontitis (PD), and recently, microRNAs (miRNAs) were associated with their progression. This review aims to assess the role of miRNAs in the pathogenesis of DM-associated PD and their plausible application as a biomarker for PD in individuals with DM. Materials and Methods: The search conducted until September 2023 on Medline (Pubmed), Scopus, Embase, and Web of Science using the keywords “microRNA,” “miRNA,” or “miR,” combined with “Diabetes” and “PD” yielded 100 articles. Only research focusing on the role of miRNAs in the pathogenesis of DM-associated PD and their potential application as biomarkers for both conditions were included. Finally, 14 studies were assessed for any bias, and the collected data included study design, sample size, participant groups, age, sample obtained, PD severity, miRNAs examined, clinical and biochemical parameters related to DM and PD, and primary outcomes. Results: In vivo studies indicated altered expression of miRNAs-146a, -146b, -155, -200b, -203, and -223, specifically in the comorbid subjects with both conditions. Animal, ex vivo, and in vitro studies demonstrated altered expression of miRNAs-126, -147, -31, -25-3p, -508-3p, -214, 124-3p, -221, -222, and the SIRT6-miR-216/217 axis. These miRNAs impact innate and adaptive immune mechanisms, oxidative stress, hyperglycemia, and insulin sensitivity, thereby promoting periodontal destruction in DM. miRNA-146a emerges as a reliable biomarker of PD in DM, whereas miRNA-155 is a consistent predictor of PD in subjects without DM. Conclusions: miRNAs exert influence on immuno-inflammation in DM-associated PD. Although they can be biomarkers of PD and DM, their clinical utility is hindered by the absence of standardized tests to evaluate their sensitivity and specificity. Moreover, there has been limited exploration of the role of miRNAs in DM-associated PD through human studies. Future clinical trials are warranted to address this gap, focusing on standardizing sample collection, miRNA sources, and detection methods. This approach will enable the identification of specific miRNAs for DM-associated PD.

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Section: Discussionmentioning

confidence: 99%

Role of microRNAs in Diabetes-Associated Periodontitis: A Scoping Review

Agnihotri,

Gaur,

Bhat

2024

J Int Soc Prev Community Dent

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“…Recent studies have suggested that alterations in regulatory microRNA (miRNA) expression may mediate the pathophysiologic features of various disease states, such as dermal inflammation, fibrosis, and immune dysregulation [ 98 ]. Expression of miR-1236 in LECs is associated with the inhibition of lymphangiogenesis via VEGFR3, Akt, and ERK downregulation [ 99 ] ( Figure 2 a).…”

Section: Lymphedema and Other Lymphatic Anomaliesmentioning

confidence: 99%

Dysregulation of Lymphatic Endothelial VEGFR3 Signaling in Disease

Kuonqui,

Campbell,

Sarker

et al. 2023

Cells

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Vascular endothelial growth factor (VEGF) receptor 3 (VEGFR3), a receptor tyrosine kinase encoded by the FLT4 gene, plays a significant role in the morphogenesis and maintenance of lymphatic vessels. Under both normal and pathologic conditions, VEGF-C and VEGF-D bind VEGFR3 on the surface of lymphatic endothelial cells (LECs) and induce lymphatic proliferation, migration, and survival by activating intracellular PI3K-Akt and MAPK-ERK signaling pathways. Impaired lymphatic function and VEGFR3 signaling has been linked with a myriad of commonly encountered clinical conditions. This review provides a brief overview of intracellular VEGFR3 signaling in LECs and explores examples of dysregulated VEGFR3 signaling in various disease states, including (1) lymphedema, (2) tumor growth and metastasis, (3) obesity and metabolic syndrome, (4) organ transplant rejection, and (5) autoimmune disorders. A more complete understanding of the molecular mechanisms underlying the lymphatic pathology of each disease will allow for the development of novel strategies to treat these chronic and often debilitating illnesses.

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“…Due to their functionally active properties and stability within vesicles, miRNAs have been extensively studied as potential biomarkers in various diseases such as Alzheimer’s [ 8 , 9 ], cancers [ 10 ], and cardiovascular diseases [ 11 , 12 ]. To our knowledge, an understanding of the role of miRNAs in secondary lymphedema remains to be explored, but evidence from related pathological conditions indicates their potential involvement [ 13 ]. For instance, miR-29 has been found to be a negative regulator of skin fibrosis, one of the hallmarks of lymphedema.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Circulating MicroRNAs and Adipokines in Breast Cancer Survivors with Arm Lymphedema

Yusof

Groen

Rosli

et al. 2022

IJMS

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Breast cancer-related lymphedema (BCRL) is a form of secondary lymphedema that is characterized by abnormal swelling of one or both arms due to the accumulation of lymph fluid in the interstitial tissue spaces, resulting from obstruction of the lymphatic vessels due to surgery insults, radiotherapy, or chemotherapy. Due to the multifactorial nature of this condition, the pathogenesis of secondary lymphedema remains unclear and the search for molecular factors associated with the condition is ongoing. This study aimed to identify serum microRNAs and adipokines associated with BCRL. Blood was collected from 113 breast cancer survivors and processed to obtain serum for small RNA-sequencing (BCRL vs. non-BCRL, n = 7 per group). MicroRNAs that were differentially expressed (fold change >1.5, p < 0.05) between lymphedema cases and those without lymphedema were further quantified in a validation cohort through quantitative reverse transcription PCR (BCRL n = 16, non-BCRL, n = 83). Leptin and adiponectin levels were measured in a combined cohort (BCRL n = 23, non-BCRL n = 90) using enzyme-linked immunosorbent assays. Two of the most significantly upregulated microRNAs, miR-199a-3p and miR-151a-3p, were strongly correlated with the onset of lymphedema and diabetes mellitus in the BCRL group. Leptin levels were higher in the BCRL cohort compared to the non-BCRL cohort (p < 0.05). A metabolic syndrome biomarker, the adiponectin/leptin ratio, was found to be lower in the BCRL group than in the non-BCRL group (median: 0.28 vs. 0.41, p < 0.05). Extensive studies on the mechanisms of the identified microRNAs and association of leptin with arm lymphedema may provide new insights on the potential biomarkers for lymphedema that should be followed up in a prospective cohort study.

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Crosstalk Between microRNAs and the Pathological Features of Secondary Lymphedema

Cited by 5 publications

References 119 publications

Role of microRNAs in Diabetes-Associated Periodontitis: A Scoping Review

Role of microRNAs in Diabetes-Associated Periodontitis: A Scoping Review

Dysregulation of Lymphatic Endothelial VEGFR3 Signaling in Disease

Evaluation of Circulating MicroRNAs and Adipokines in Breast Cancer Survivors with Arm Lymphedema

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