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Crosstalk Between microRNAs and the Pathological Features of Secondary Lymphedema

ABSTRACT: Secondary lymphedema is characterized by lymphatic fluid retention and subsequent tissue swelling in one or both limbs that can lead to decreased quality of life. It often arises after loss, obstruction, or blockage of lymphatic vessels due to multifactorial modalities, such as lymphatic insults after surgery, immune system dysfunction, deposition of fat that compresses the lymphatic capillaries, fibrosis, and inflammation. Although secondary lymphedema is often associated with breast cancer, the condition can occur in patients with any type of cancer that requires lymphadenectomy such as gynecological, genitourinary, or head and neck cancers. MicroRNAs demonstrate pivotal roles in regulating gene expression in biological processes such as lymphangiogenesis, angiogenesis, modulation of the immune system, and oxidative stress. MicroRNA profiling has led to the discovery of the molecular mechanisms involved in the pathophysiology of auto-immune, inflammation-related, and metabolic diseases. Although the role of microRNAs in regulating secondary lymphedema is yet to be elucidated, the crosstalk between microRNAs and molecular factors involved in the pathological features of lymphedema, such as skin fibrosis, inflammation, immune dysregulation, and aberrant lipid metabolism have been demonstrated in several studies. MicroRNAs have the potential to serve as biomarkers for diseases and elucidation of their roles in lymphedema can provide a better understanding or new insights of the mechanisms underlying this debilitating condition.

SUBMITTER: Yusof K

PROVIDER: S-EPMC8558478 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:MicroRNAs (miRNAs/miRs) are small non‑coding RNAs (ncRNAs) that regulate gene expression. Emerging knowledge has suggested that miRNAs have a role in the pathogenesis of metabolic disorders, supporting the hypothesis that miRNAs may represent potential biomarkers or targets for this set of diseases. However, the current evidence is often controversial. Therefore, the aim of the present study was to determine the associations between miRNAs‑target genes, miRNA‑long ncRNAs (lncRNAs), and miRNAs‑small molecules in human metabolic diseases, including obesity, type 2 diabetes and non‑alcoholic fatty liver disease. The metabolic disease‑related miRNAs were obtained from the Human MicroRNA Disease Database (HMDD) and miR2Disease database. A search on the databases Matrix Decomposition and Heterogeneous Graph Inference (MDHGI) and DisGeNET were also performed. miRNAs target genes were obtained from three independent sources: Microcosm, TargetScan and miRTarBase. The interactions between miRNAs‑lncRNA and miRNA‑small molecules were performed using the miRNet web tool. The network analyses were performed using Cytoscape software. As a result, a total of 20 miRNAs were revealed to be associated with metabolic disorders in the present study. Notably, 6 miRNAs (miR‑17‑5p, miR‑29c‑3p, miR‑34a‑5p, miR‑103a‑3p, miR‑107 and miR‑132‑3p) were found in the four resources (HMDD, miR2Disease, MDHGI, and DisGeNET) used for these analyses, presenting a stronger association with the diseases. Furthermore, the target genes of these miRNAs participate in several pathways previously associated with metabolic diseases. In addition, interactions between miRNA‑lncRNA and miRNA‑small molecules were also found, suggesting that some molecules can modulate gene expression via such an indirect way. Thus, the results of this data mining and integration analysis provide further information on the possible molecular basis of the metabolic disease pathogenesis as well as provide a path to search for potential biomarkers and therapeutic targets concerning metabolic diseases.

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Crosstalk Between microRNAs and the Pathological Features of Secondary Lymphedema

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