Association between circulating micro-ribonucleic acids and metabolic syndrome in older adults from a population-based study.

BACKGROUND AND AIMS: Aging is a major factor in development of chronic non-communicable diseases (NCD). Epigenetic causes are risk factors in NCD development since studies indicate that the expression of micro-ribonucleic acids (miRs) is altered under different clinical conditions. This study aimed to analyze the expression profile of circulating miRs and investigate their association with biomarkers of cardiometabolic risk in older adults living in São Paulo municipality, Brazil. METHODS: A cross-sectional study was conducted based on the analysis of data from 200 older adults, with a mean age of 69.1 (0.5) years old participating in the ISA-Nutrition. The expression profiles of 21 plasma miRs related to glycemic and lipid metabolism, adiposity, and inflammation were evaluated in relation to cardiometabolic risk. Individuals were distributed into groups according to diagnosis of metabolic syndrome (MetS). The Stata Somersd module was used to calculate confidence intervals for Kendall's tau-a to estimate the correlations among variables. RESULTS: Differences in the plasma expression were observed in two of the 21 miRs evaluated according to the MetS presence in participants. Individuals with MetS showed higher expression of miR-30a and miR-122 than individuals without MetS. CONCLUSIONS: Considering that miR-30, and miR-122 were altered due to MetS, these miRs may be potential biomarkers for MetS in older adults.

Circulating MiRNAs Are Associated With Low-grade Systemic Inflammation and Leptin Levels in Older Adults.

Inflammaging refers to the low-grade systemic inflammation that occurs with aging present in chronic non-communicable diseases. MicroRNAs (miRNAs) are potential biomarkers for these diseases in older adults. This study aimed to assess the expression of 21 circulating miRNAs and their associations with inflammatory biomarkers in older adults. This cross-sectional study was performed with 200 individuals participating in ISA-Nutrition. The systemic low-grade inflammation score (SIS) was calculated from the plasma concentration of 10 inflammatory biomarkers. Circulating miRNA expression was assessed using the Fluidigm method. Wilcoxon-Mann-Whitney test was employed to determine differences in SIS among groups distributed according to sex and presence of MetS. Spearman's correlation was used to estimate correlations among SIS, leptin levels, miRNA expression, and variables of interest. Analyses were performed using software R version 4.2.3, with a significance level of 0.05. The final sample consisted of 193 individuals with a mean age of 69.1 (SE = 0.5) years, being 64.7% individuals with metabolic syndrome (MetS). Positive correlations were observed between leptin concentration and metabolic risk factors, and leptin concentration was higher in individuals with MetS compared to those without MetS. The expression of 15 circulating miRNAs was negatively correlated with leptin concentration. GLMs showed negative associations between miRNAs (miR-15a, miR-16, miR-223, miR-363, miR-532), leptin, and/or SIS values; and only miR-21 showed positive association with SIS values. The results suggest the presence of peripheral leptin resistance associated with low-grade inflammation and plasma expression of miRNAs in older adults. These findings suggest the potential role of miRNAs as biomarkers for cardiometabolic risk.

Expression of Circulating MicroRNAs Associated with Obesity and their Relationships with Biochemical Parameters and Health-related Physical Fitness in Children 6 to 10 Years Old in Cali, Colombia.

BACKGROUND: Obesity is a public health problem worldwide; it has reached pandemic proportions in the last 40 years. Its prevalence in children and adolescents increased from 0.7% to 7.8% between 1975 and 2016. Recently, microRNAs (miRNAs) have been reported as regulatory factors related to molecular functions under different conditions. These can be used as biomarkers of a disease to estimate risks in the early stages. OBJECTIVE: This study aimed to determine the expression levels of miRNAs associated with childhood obesity and their relationships with biochemical parameters and Health-related Physical Fitness (HRPF). METHODS: This was a descriptive cross-sectional study in which a population of 40 children between 6 and 10 years of age of both sexes from Cali, Colombia, was evaluated; the children were classified as 20 normal-weight and 20 obese. Blood biochemistry, HRPF, and miRNA expression levels were determined (hsa-miR-122-5p, hsa-miR-15b-5p, hsa-miR-191-5p, hsa-miR-486-3p, hsa-miR-222-3p. Comparisons were made between the groups, miRNA associations between the studied variables, and linear regression analysis. RESULTS: Twenty normal-weight and 20 obese patients were evaluated. Both groups had an average age of eight years old. The miRNA hsa-miR-122-5p (p < 0.05) was overexpressed in the obese group. According to the linear regression analysis, the amount of adipose tissue may be associated with the production of miRNAs (hsa-miR-15b-5p, hsa-miR-222-3p, hsa-miR-122-5p, and hsamiR- 191-5p). CONCLUSION: Four miRNAs (hsa-miR-15b-5p, hsa-miR-222-3p, hsa-miR-122-5p, and hsa-miR- 191-5p) are associated with modifications in biochemical variables of HRPF in this group. Adipose tissue mass could be associated with the production of these miRNAs, thus making them biomarkers of childhood obesity risk.

Systematic review of circulating MICRORNAS as biomarkers of cervical carcinogenesis.

BACKGROUND: Cervical cancer is a preventable disease, but it is a major public health problem despite having a good prognosis when diagnosed early. Although the Pap smear has led to huge drops in rates of cervical cancer and death from the disease, it has some limitations, making new approaches necessary for early diagnosis and biomarkers discovery. MiRNAs have been considered a new class of non-invasive biomarkers and may have great clinical value for screening early-stage cervical intraepithelial neoplasia. Well-designed studies have emerged as a necessary strategy for the identification of miRNAs that could be used safely and reliably for a differential diagnosis. This review aims to provide an up-to-date perspective on the assessment of circulating miRNA expression from precursor lesions to cervical cancer, identifying circulating miRNAs or specific miRNA signatures that can be used as potential biomarkers of different stages of cervical carcinogenesis. METHODS: A systematic review was performed and searches were conducted in the PubMed, LILACS, and Scopus electronic databases. RESULTS: Most studies involved Chinese ethnic women and searched for circulating miRNAs in serum samples. Thirty three microRNAs were evaluated in the eligible studies and 17 (miR-196a, miR-16-2, miR-497, miR-1290, miR-425-5p, hsa-miR- 92a, miR-1266, miR-9, miR-192, miR-205, miR-21, miR-152, miR-15b, miR-34a, miR-218, miR-199a-5p and miR-155-5p) showed up-regulation in women with precursor lesion and cervical cancer and 16 microRNAs showed decreased expression in these same groups of women compared to healthy controls (miR-195, miR-2861, miR-145, miR-214, miR-34a, miR-200a, let-7d-3p, miR-30d-5p, miR-638, miR-203a-3p, miR-1914-5p, miR-521, miR-125b, miR-370, miR-218 and miR-100). CONCLUSION: Therefore, defining promising circulating miRNAs or specific miRNA signatures of biological fluid samples can be useful for the screening, diagnosis, prognosis and clinical monitoring of women undergoing cervical carcinogenesis, but greater standardization of studies seems to be necessary for greater consolidation of information.

Serum miRNAs miR-140-3p and miR-23b-3p as potential biomarkers for osteoporosis and osteoporotic fracture in postmenopausal Mexican-Mestizo women.

Osteoporosis is a metabolic bone disorder characterized by low bone mineral density and decreased bone strength, leading to an increased risk of fractures with a consequent increase in morbidity and mortality. The current methods to estimate the fracture risk are very limited. microRNAs (miRNAs) have been considered as good biomarkers for many pathological processes, including osteoporosis. Some circulating miRNAs are associated with regulation of bone formation and differentiation of bone cells. The aim of this study, was to analyze the expression of miRNAs in serum of patients with osteoporosis (n = 20) and healthy controls (n = 20). Expression of 754 miRNAs was analyzed through quantitative real time RT-PCR arrays. Seven miRNAs showed significant differences between groups. The microRNAs miR-23b-3p, miR-140-3p and miR-885-5p were selected based on fold change and p-values (40.5, p = 0.038, 20.7, p = 0.045, and 2.2, p = 0.002; respectively) for validation in independent serum samples from patients with osteopenia (n = 28), osteoporosis (n = 26) and osteoporotic hip fracture (n = 21). After validation, we confirm differences across the groups for miR-23b-3p and miR-140-3p. Our data pointed miR-140-3p and miR-23b-3p as potential biomarkers candidates for osteoporosis in postmenopausal women.

Plasma levels of increased miR-195-5p correlates with the sFLT-1 levels in preeclampsia.

Although the role of soluble fms-like tyrosine kinase 1 (sFLT-1) in preeclampsia is well-established, the mechanism related to its synthesis remains poorly understood. We evaluated the association among the circulating microRNAs (miRs) and sFLT-1 levels in preeclampsia pregnant women. For this purpose, we measured the plasma sFLT-1 levels in 24 preeclampsia women and selected from these, three subjects with the lowest and three with the highest levels of sFLT-1 in order to screen for potential miRs associated with plasmatic sFLT-1 concentrations using a polymerase chain reaction-array (PCR-array) methodology. From screening results, we found three statistically different expressed miRs with fold change (FC-high/low levels) ≥3.0: miR-195-5p (FC = 5.2 increase in group with high sFLT-1 levels), miR-16-5p (FC = 3.2; increase in group with high sFLT-1 levels), and miR-375 (FC = -3.0; decrease in group with high sFLT-1 levels) which were later validated in all samples (n = 24). To correlate these miRs and plasma sFLT-1 levels, we used two extremes of analysis. In one part, we compared 12 preeclampsia women with the lowest sFLT-1 levels (L-50% group) to 12 with the highest levels (50% H group); and in the second analysis, 6 preeclampsia women (L-25%) from the L group to 6 preeclampsia women from the H group (H-25%). Our results showed increased expression of miR-195-5p in the H group, considering both the analyses with 50%, FC = 2.1 and 25%, FC = 4.2. Regarding other miRs, lack of correlation was found in both analyses (50% and 25%). In conclusion, our data demonstrate an association of higher levels of sFLT-1 with increased expression of miR-195-5p in preeclampsia pregnant women.

Circulating microRNAs as potential cancer biomarkers / MicroRNA circulantes como potenciales biomarcadores en cáncer

Cancer is currently recognized as a major cause of mortality worldwide, and, as such, has a significant impact on public health. Successful early detection strategies are linked to a decrease in mortality; however, because they are invasive, highly complex, and have low specificity, their application has been limited. MicroRNAs (miRNAs) are short, non-coding RNA sequences capable of regulating gene expression. Molecular mechanisms of miRNAs in cancer are not fully understood, but specific patterns of miRNAs expression have been associated with many tumour types. MicroRNAs as biomarkers can help to identify tumour origin and allow their early detection. They can also be used to monitor progression and therapeutic response. The presence and stability of miRNAs in blood, as circulating miRNAs, are major factors that contribute to their use as potential biomarkers in a clinical context. The aim of this article is to present a review of miRNAs as circulating biomarkers in cancer.

El cáncer es reconocido como una de las principales causas de mortalidad a nivel mundial teniendo así un impacto significativo en la salud pública. Una disminución en la mortalidad por esta enfermedad se ha asociado con estrategias exitosas de detección temprana; sin embargo, debido a que estas son invasivas, altamente complejas y registran baja especificidad, su aplicación ha sido limitada. Los microRNA (miRNA) son RNA no codificantes de secuencias cortas, capaces de regular la expresión génica. Los mecanismos moleculares de los miRNA en cáncer aún no están totalmente clarificados, pero patrones específicos de la expresión de estos han sido asociados con muchos tipos de tumores. Los miRNA como biomarcadores pueden ayudar a identificar el origen de un tumor, realizar detección temprana, predecir la progresión de la enfermedad y la respuesta al tratamiento. La presencia y estabilidad de los miRNA en la sangre, como miRNA circulantes, son los principales factores que contribuyen a su uso potencial como biomarcadores en un contexto clínico. El objetivo de este artículo es realizar una revisión sobre los miRNA circulantes en cáncer.

Reduced circulating miR-196b levels is associated with preeclampsia.

MicroRNAs (miRs) are small noncoding RNAs, highly stable in plasma, that regulate gene expression by base-pairing to the 3'-untranslated region of target mRNAs. We compared the expression of 3 circulating miRs (miR-125b, miR-146a, and miR-196b), which is related to the control of cell proliferation, differentiation, and apoptosis in preeclamptic (n=19) and healthy pregnant women (n=14). We found that women with preeclampsia (PE) presented lower expression of miR-196b (-2.9-fold change). The other miRs were at similar levels. This study is the first to demonstrate this difference, and highlights new opportunities for investigation into the role of miRs in PE.