Circulating miRNAs and miRNA shuttles as biomarkers: Perspective trajectories of healthy and unhealthy aging

Olivieri, Fabiola; Capri, Miriam; Bonafè, Massimiliano; Morsiani, Cristina; Jung, Hwa Jin; Spazzafumo, Liana; Viña, José; Suh, Yousin

doi:10.1016/j.mad.2016.12.004

Cited by 101 publications

(78 citation statements)

References 83 publications

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“…MicroRNAs (miRNAs) are a type of small (~22-nt long), non-coding RNA molecules that regulate target gene expression by translational inhibition or mRNA destabilization through the combination with the 3'-untranslated region of target messenger RNAs. The loss of homeostasis in the miRNA/mRNA axis leads to a number of physiological and pathological events, such as inflammation, senescence and tumorigenesis (1,2).…”

Section: Introductionmentioning

confidence: 99%

miR‑186 functions as a tumor suppressor in osteosarcoma cells by suppressing the malignant phenotype and aerobic glycolysis

Xiao

Wei

et al. 2018

Oncol Rep

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Osteosarcoma (OS) is the most common primary bone malignancy among children and adolescents. Deregulation of microRNAs has been well documented in OS, while the putative effects of miR‑186 have not been identified yet. In the present study, we assessed the expression of miR‑186 in a cohort of 40 OS tissues and explored its effects on OS cells. As expected, miR‑186 was suppressed in OS tissues compared with relative normal tissues. Overexpression of miR‑186 inhibited cell proliferation, arrested the cell cycle progression and suppressed the cell invasion of the HOS and U2 OS cell lines. These results indicated the tumor‑suppressive role of miR‑186 in OS. Among the target genes of miR‑186, we found that pituitary tumor transforming gene 1 (PTTG1) may be a target gene of miR‑186 in OS and that the overexpression of PTTG1 could partially abolish miR‑186‑mediated suppressive effects on OS cells. Aerobic glycolysis is the major way of energy supply and is one of the characteristic phenotypes of tumor cells. In addition, we found that overexpression of miR‑186 significantly suppressed the expression of hypoxia‑inducible factor 1 (HIF‑1) and inhibited the glucose uptake and lactate production of OS cells. Collectively, our findings demonstrated that miR‑186 functions as a tumor suppressor in OS cells partially by targeting PTTG1 and that HIF‑1‑mediated suppression of aerobic glycolysis may be also involved in its suppressive effects.

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Section: Introductionmentioning

confidence: 99%

miR‑186 functions as a tumor suppressor in osteosarcoma cells by suppressing the malignant phenotype and aerobic glycolysis

Xiao

Wei

et al. 2018

Oncol Rep

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“…Yang et al demonstrated that miR-598 suppressed the invasion and migration in NSCLC as a tumor suppressor through negatively regulate Derlin-1 (DERL1) and epithelial-mesenchymal transition (EMT) [10]. However, the roles of genes and miRNAs in NSCLCs are still not well understood [11].…”

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confidence: 99%

Microarray data analysis on gene and miRNA expression to identify biomarkers in non-small cell lung cancer

et al. 2020

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Background: The aim of this study was to gain further investigation of non-small cell lung cancer (NSCLC) tumorigenesis and identify biomarkers for clinical management of patients through comprehensive bioinformatics analysis. Methods: miRNA and mRNA microarray datasets were downloaded from GEO (Gene Expression Omnibus) database under the accession number GSE102286 and GSE101929, respectively. Genes and miRNAs with differential expression were identified in NSCLC samples compared with controls, respectively. The interaction between differentially expressed genes (DEGs) and differentially expressed miRNAs (DEmiRs) was predicted, followed by functional enrichment analysis, and construction of miRNA-gene regulatory network, protein-protein interaction (PPI) network, and competing endogenous RNA (ceRNA) network. Through comprehensive bioinformatics analysis, we anticipate to find novel therapeutic targets and biomarkers for NSCLC. Results: A total of 123 DEmiRs (5 up-and 118 down-regulated miRNAs) and 924 DEGs (309 up-and 615 down-regulated genes) were identified. These genes and miRNAs were significantly involved in different pathways including adherens junction, relaxin signaling pathway, and axon guidance. Furthermore, hsa-miR-9-5p, has-miR-196a-5p and hsa-miR-31-5p, as well as hsa-miR-1, hsa-miR-218-5p and hsa-miR-135a-5p were shown to have higher degree in the miRNA-gene regulatory network and ceRNA network, respectively. Furthermore, BIRC5 and FGF2, as well as RTKN2 and SLIT3 were hubs in the PPI network and ceRNA network, respectively. Conclusion: Several pathways (adherens junction, relaxin signaling pathway, and axon guidance) miRNAs (hsa-miR-9-5p, has-miR-196a-5p, hsa-miR-31-5p, hsa-miR-1, hsa-miR-218-5p and hsa-miR-135a-5p) and genes (BIRC5, FGF2, RTKN2 and SLIT3) may play important roles in the pathogenesis of NSCLC.

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“…Attaining this goal clearly requires more accurate and possibly more numerous biomarkers of biological aging capable of predicting functional capacity at a later age than chronological age. Since the variance of aging phenotypes widens over time, owing to different individual trajectories of aging (Ferrucci et al, 2020;Olivieri et al, 2017), immunological/biological age rather than chronological age appears to be a more sensitive approach also to assess individual susceptibility to the adverse outcomes of COVID-19 infection. Consequently, a panel of biomarkers of immunological/biological aging could help identify subjects at risk of adverse COVID-19 outcomes also among the younger population.…”

Section: Potential Implications For Sars-cov-2 Host-directed Therapiesmentioning

confidence: 99%

Inflamm-Aging: Why Older Men Are the Most Susceptible to SARS-Cov-2 Complicated Outcomes

Bonafè

Prattichizzo

Giuliani

et al. 2020

Preprint

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is characterized by a high mortality of elderly men with age-related comorbidities. In most of these patients, uncontrolled local and systemic hyperinflammation induces severe and often lethal outcomes. The aging process is characterized by the gradual development of a chronic subclinical systemic inflammation (inflamm-aging) and by acquired immune system impairment (immune senescence). Here, we advance the hypothesis that some key features of aging contribute to the disproportionate SARS-CoV-2 mortality suffered by elderly men. At least four well-recognized aging-related characteristics that are strongly expressed in older men go some way towards explaining why these patients account for the vast majority of fatalities: i. the presence of subclinical systemic inflammation without overt disease, ii. a blunted acquired immune system and type I interferon response due to the chronic inflammation; iii. the downregulation of ACE2 (SARS-CoV-2 receptor), which triggers inflammation, particularly in patients with age-related comorbid diseases such as type II diabetes; and iv. accelerated biological aging, as measured by epigenetic and senescence markers (e.g. telomere shortening) associated to the chronic inflammatory state. Though typical of the aged, especially of elderly men, it is conceivable that these features are also shared by some subsets of the younger population. The high mortality rate of SARS-CoV-2 infection suggests that clarification of the mechanisms of inflamm-aging and immune senescence can help combat not only age-related disorders but also SARS-CoV-2 infection.

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Circulating miRNAs and miRNA shuttles as biomarkers: Perspective trajectories of healthy and unhealthy aging

Cited by 101 publications

References 83 publications

miR‑186 functions as a tumor suppressor in osteosarcoma cells by suppressing the malignant phenotype and aerobic glycolysis

miR‑186 functions as a tumor suppressor in osteosarcoma cells by suppressing the malignant phenotype and aerobic glycolysis

Microarray data analysis on gene and miRNA expression to identify biomarkers in non-small cell lung cancer

Inflamm-Aging: Why Older Men Are the Most Susceptible to SARS-Cov-2 Complicated Outcomes

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