miR-155 Levels Research Articles

Tumor Suppressor miR-34a: Potential Biomarker of TACE Response in HCC.

TACE induces variable systemic effects by producing factors that promote inflammation, oncogenesis, and angiogenesis. Here we compare concentrations of microRNAs (miR-21, miR-210 and miR-34a) and vascular endothelial growth factor (VEGF) in hepatocellular carcinoma (HCC) patients undergoing TACE with degradable (DSM) and nondegradable (DEB) particles and potential use of these biomarker changes for prediction of patient outcomes. Overall, 52 patients with HCC treated with DSM TACE (24 patients) and DEB TACE (28 patients) were included in this prospective study. Concentrations of studied biomarkers were measured from blood plasma preprocedurally, immediately (< 90min) postprocedurally, and 24-h after TACE. Levels were compared between DSM and DEB TACE and correlated with treatment response six and 12months after the first TACE. Both DSM and DEB TACE elevated plasma levels of miR-21, miR-34a, and miR-210 at 24h post-procedure compared to baseline levels (FC 1.25-4.0). MiR-34a elevation immediately after TACE was significantly associated with nonprogressive disease compared to those with progressive disease at both sixmonths (FCa: p = 0.014) and 12months (FCa: p = 0.029) post-TACE. No significant biomarker changes were found between the embolization particle groups. However, VEGF levels showed a decrease only in the DSM TACE group (FC24: p = < 0.001). Embolization particle type did not significantly impact miRNA or VEGF changes post-TACE. However, miR-34a elevation immediately after the procedure predicts better patient outcome and may prove useful as a biomarkers for the monitoring of clinical outcomes. Level 3 Prospective cohort study.

MiR-1, miR-133a, miR-29b and skeletal muscle fibrosis in chronic limb-threatening ischaemia.

Chronic limb-threatening ischaemia (CLTI), the most severe manifestation of peripheral arterial disease (PAD), is associated with a poor prognosis and high amputation rates. Despite novel therapeutic approaches being investigated, no significant clinical benefits have been observed yet. Understanding the molecular pathways of skeletal muscle dysfunction in CLTI is crucial for designing successful treatments. This study aimed to identify miRNAs dysregulated in muscle biopsies from PAD cohorts. Using MIcroRNA ENrichment TURned NETwork (MIENTURNET) on a publicly accessible RNA-sequencing dataset of PAD cohorts, we identified a list of miRNAs that were over-represented among the upregulated differentially expressed genes (DEGs) in CLTI. Next, we validated the altered expression of these miRNAs and their targets in mice with hindlimb ischaemia (HLI). Our results showed a significant downregulation of miR-1, miR-133a, and miR-29b levels in the ischaemic limbs versus the contralateral non-ischaemic limb. A miRNA target protein-protein interaction network identified extracellular matrix components, including collagen-1a1, -3a1, and -4a1, fibronectin-1, fibrin-1, matrix metalloproteinase-2 and -14, and Sparc, which were upregulated in the ischaemic muscle of mice. This is the first study to identify miR-1, miR-133a, and miR-29b as potential contributors to fibrosis and vascular pathology in CLTI muscle, which supports their potential as novel therapeutic agents for this condition.

Abstract A007: Characterization of miR-141 and miR-145 expression in cancer stem cells of metastatic prostate cancer patients

Abstract Background: Prostate cancer (PCA) is the second most prevalent cancer globally and the fifth leading cause of cancer-related mortality. However, effective prognostic biomarkers for metastatic PCA remain lacking. Recent research highlights the role of microRNAs (miRNAs) in regulating cancer stem cells (CSCs) and influencing tumour progression across various cancers. Therefore, in this we investigated the effects of miR-141 and miR-145 expression on the metastatic PCA of CSCs and assessed their potential role as biomarkers for metastatic PCA prognosis. Methods: The expression levels of miR-141 and miR-145 were quantified using real-time qPCR. Flow cytometry was employed to assess the levels of prostate cancer stem cells (PCSCs) in tissue samples from patients with localized (non-metastatic) and metastatic PCA. Results: Our findings revealed a significant increase in miR-141 expression, accompanied by elevated levels of CD44^high/CD24^low and CD133^high, in metastatic PCA compared to localized PCA. Conversely, reduced miR-145 expression was associated with enhanced stemness characteristics, as indicated by increased CD44^high/CD24^low and CD133^high levels, in metastatic PCA compared to localized PCA. Additionally, prostate-specific antigen (PSA) and testosterone levels exhibited a significant rise (p&amp;lt;0.001), while apoptosis rates decreased in both localized and metastatic PCA compared to localized PCA. Conclusions: The collective findings of this study suggest that miR-141 and miR-145, in conjunction with CSC markers, hold promise as diagnostic and prognostic tools for PCA. They may also be valuable for detecting minimal residual disease and improving therapeutic strategies for managing metastatic PCA. Citation Format: Kamla Kant Shukla, Gautam Ram Choudhary. Characterization of miR-141 and miR-145 expression in cancer stem cells of metastatic prostate cancer patients [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: RNAs as Drivers, Targets, and Therapeutics in Cancer; 2024 Nov 14-17; Bellevue, Washington. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(11_Suppl):Abstract nr A007.

The circulatory levels and bone expression of MIR21, 34a, 155 and their target genes in a section of Egyptian Population

Bone tissue is constantly regenerated and repaired through a finely balanced process known as bone remodeling. Many miRNAs act as regulators of the signaling pathways involved in bone metabolic processes to maintain tissue homeostasis. This study aimed to assess the circulating levels of MIR21, MIR34a, and MIR155 in human serum and their bone expression, and the expression of bone turnover-related genes which can reflect the bone quality. This prospective study was conducted on 60 patients (30 males and 30 females) indicated for surgical interventions for neural decompression +/- fixation. Relative quantification of expression of MIR21, miR34a, and MIR155 and bone related genes was assayed using PCR. The serum levels of osteocalcin and Serum Bone Alkaline Phosphatase (sBAP) were assayed using a human ELISA kit. The main finding of the present work was the strong positive association between the circulating levels of only miR21 and MIR155 and their bone expression in the population under study and with bone markers and target genes Also, a positive association was found between both bone expression and circulating MIR21 levels with age and sBAP. These results suggest that the circulating levels of these microRNAs as early markers for the predication of bone quality.

Extracellular vesicle transfer of miR-1 to adipose tissue modifies lipolytic pathways following resistance exercise.

Extracellular vesicles (EVs) have emerged as important mediators of intertissue signaling and exercise adaptations. In this human study, we provide evidence that muscle-specific microRNA-1 (miR-1) was transferred to adipose tissue via EVs following an acute bout of resistance exercise. Using a multimodel machine learning automation tool, we discovered muscle primary miR-1 transcript and CD63+ EV count in circulation as top explanatory features for changes in adipose miR-1 levels in response to resistance exercise. RNA-Seq and in-silico prediction of miR-1 target genes identified caveolin 2 (CAV2) and tripartite motif containing 6 (TRIM6) as miR-1 target genes downregulated in the adipose tissue of a subset of participants with the highest increases in miR-1 levels following resistance exercise. Overexpression of miR-1 in differentiated human adipocyte-derived stem cells downregulated these miR-1 targets and enhanced catecholamine-induced lipolysis. These data identify a potential EV-mediated mechanism by which skeletal muscle communicates with adipose tissue and modulates lipolysis via miR-1.

MicroRNAs as potential biomarkers of response to modified Atkins diet in treatment of adults with drug-resistant epilepsy: A proof-of-concept study

BackgroundAccurate predictors of response to modified Atkins diet (MAD) are needed. MicroRNAs are potential biomarkers in epilepsy. This study aimed to explore the value of circulating miR-146a, miR-155, miR-22, miR-21 and miR-134 levels in predicting response to MAD. MethodsPatients who completed 3 months of MAD were selected from a prospective cohort of adults with DRE followed in a specialized MAD outpatient clinic. Patients were classified as responders if any reduction in seizure frequency at follow-up, calculated through seizure-calendars). The >50 % seizure reduction cut-off was also explored. Qualitative benefits in seizures and cognition were analysed. Blood samples were collected prior to initiate MAD and microRNAs were quantified by qRT-PCR. ResultsThirty-nine patients were included (56 %males, mean age=33.1±8.5yo, 62 %focal epilepsies, 59 %structural aetiology): 20(51 %) were responders [mean reduction in seizure frequency=54 %(17–100 %); 10 had ≥50 % reduction]; 25(64 %) reported qualitative benefit in seizures and 21(54 %) reported cognitive benefits. At pre-treatment baseline, a panel combining serum levels of all studied microRNAs predicted seizure reduction (AUC=0.839, p<0.0001), qualitative benefit in seizures (AUC=0.683, p=0.048) and in cognition (AUC=0.751, p<0.01) at 3months. miR-146a was the only significant microRNA when evaluated in isolation. There was no statistical correlation in the biomarkers when a ≥50 % seizure reduction was compared to <50 %. ConclusionsA panel combining pre-treatment serum levels of miR-146a, miR-155, miR-134, miR-21 and miR-22 predicted any reduction in seizures with MAD in adults with DRE at 3months. This panel may be a promising biomarker and a useful tool in the selection of patients.

The levels and clinical significance of serum miR-146a, miR-145, Th17/Treg in children with respiratory syncytial virus infection pneumonia

To investigate the levels and clinical significance of serum microRNA (miR)-146a, miR-145, T-helpertype17 (Th17)/regulatory T cell (Treg) in children with respiratory syncytial virus (RSV) infectious pneumonia. The clinical data of 200 children with RSV infectious pneumonia admitted to Nantong Maternal and Child Health Hospital from June 2020 to June 2023 were retrospectively collected as the study group. At the same time, 200 children with mycoplasma pneumonia were selected as the common pneumonia group and 200 healthy children were selected as the healthy group. The levels of serum inflammatory factors [interleukin-6 (IL-6), interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α)] were detected by enzyme-linked immunosorbent assay. The expression levels of serum miR-146a and miR-145 were detected by RT-qPCR. The levels of Th17/Treg were detected by flow cytometry. The levels of miR-146a, miR-145, Th17/Treg and serum inflammatory factors were compared among the three groups. Pearson method was used to analyze the correlation between miR-146a, miR-145, Th17/Treg and serum inflammatory factors in children with RSV infectious pneumonia. The receiver operating characteristic (ROC) curve was drawn to analyze the diagnostic value of miR-146a, miR-145, Th17/Treg in children with respiratory syncytial virus infection pneumonia. The results showed that in the study group, miR-146a (2.01±0.58), miR-145 (1.81±0.46), Th17/Treg (1.09±0.31), IL-6 (7.82±2.11) ng/L and TNF-α (9.82±2.96) ng/L were higher than those in the common pneumonia group miR-146a (1.49±0.42), miR-145 (1.43±0.31), Th17/Treg (0.77±0.24), IL-6 (5.89±1.32) ng/L, TNF-α (7.34±2.32) ng/L and healthy group miR-146a (1.25±0.19), miR-145 (1.19±0.16), Th17/Treg (0.38±0.09), IL-6 (4.52±1.04) ng/L, TNF-α (5.39±1.07)ng/L. The levels of the above indexes in the common pneumonia group were higher than those in the healthy group, and the differences were statistically significant (F=183.543, 175.938, 617.182, 226.657, 193.459, P<0.05). In the study group, IFN-γ (14.18±3.25) pg/ml was lower than that in the control group (19.52±5.13) pg/ml, but higher than that in the healthy group (9.77±2.40) pg/ml, and the difference was statistically significant (F=335.432, P<0.05). Pearson correlation analysis showed that miR-146a, miR-145 and Th17/Treg were positively correlated with IL-6 and TNF-α (P<0.05), but negatively correlated with IFN-γ (P<0.05). ROC curve results showed that the area under the curve (AUC) of miR-146a, miR-145 and Th17/Treg in the diagnosis of RSV infectious pneumonia was 0.767, 0.762 and 0.790, respectively, while the combined detection of the three was 0.904. In conclusion, the levels of miR-146a, miR-145 and Th17/Treg are highly expressed in children with RSV infectious pneumonia, and are closely related to the inflammatory response of children. The combined detection of the three may have certain application value in the auxiliary diagnosis of RSV infectious pneumonia.

Characteristics of Pulmonary Inflammation in Patients with Different Forms of Active Tuberculosis.

Targeted treatment of tuberculosis-associated lung damage requires an understanding of the precise mechanisms of immunopathology. A major obstacle to the longitudinal study of tuberculosis (TB) immunopathogenesis in humans is the lack of serial lung biopsies during disease progression and treatment, which could be used to characterize local immune pathways involved in tissue damage. Understanding of the immunobiology of lung tissue damage in tuberculosis has largely been based on animal models. Our study looked for signs of inflammation in TB patients' lung biopsies. Results were compared between a site of infection and relatively healthy tissue outside the site. The most significant differences in the expression of microRNAs (miRs) and cytokine/chemokines were observed between the non-decayed tuberculoma and the surrounding parenchyma. In addition, these parameters showed almost no differences between the cavitary wall and surrounding tissue. This is an indication that the inflammatory process is more prevalent in fibrotic cavitary tuberculosis (FCT). In FCT subjects, no difference was observed between the cavity wall and the parenchyma in the production of key inflammatory factors such as IL-6, IL-11, IL-17, and IFNγ. This is an indication that the limits of the inflammatory response are broader in FCT. The expression levels of miR-191, miR-193a, miR-222, miR-223, miR-18, miR-155, miR-376c, miR-26a, miR-150, and miR-124 were not significantly different between the cavernous wall and lung tissue in patients with FCT, further confirming the spread of inflammatory and destructive processes beyond the focus of infection.

Circulating microRNA-21, microRNA-122, and microRNA-222 as diagnostic biomarkers for hepatitis c virus-related hepatocellular carcinoma

Background and aimMicroRNAs (miRs) are now a well-known subject in various tumor genesis and are studied as early diagnostic biomarker. Many arrays of miRs were incorporated in the pathogenesis of HCV-related hepatocellular carcinomas (HCV-HCC). In this respect, we aimed to evaluate the diagnostic role of circulating miR-21, miR-122, and miR-222 in Egyptian patients with HCV-HCC.Patient and methodsBetween June 2018 and April 2019, a cross-sectional comparative study was designed to evaluate the circulating miR-21, miR-122, and miR-222 by quantitative Real-Time PCR. For analytical purposes, patients were categorized into three groups: chronic HCV group (CHC-group, n = 22), HCV-related liver cirrhosis (LC-group, n = 22), and HCV-related hepatocellular carcinoma (HCV-HCC-group, n = 54).ResultsSerum levels of miR-21 and miR-222 increased with the progressive course from CHC to LC and HCC; p < .001. Serum levels of miR-122 in HCC patients were significantly lower than non-HCC patients (CHC and LC patients, n = 44); p < .001. However, the differences in levels of serum miR-122 between CHC and LC were not statistically significant; P = 0.8.ROC curve analysis showed that the sensitivity and specificity of miR-21 were 61.1% and 95.5%, miR-222 were 71.7% and 93.2%, and miR-122 were 98.2% and 100%. The positive predictive value for miRNA-21, miRNA-122, and miRNA-222 were 13.4%, 93.3%, and 10.5% respectively. The Negative predictive value for miRNA-21, miRNA-122, and miRNA-222 were 94.3%, 97.8%, and 92.7% respectively.ConclusionMiR-21 and miR-222 could be potential markers for advanced liver damage, while miR-122 had the best diagnostic accuracy and could be a promising marker for detection of HCC.

Characterisation of plasma proteins and circulating microRNAs in out-of-hospital cardiac arrest patients - approaches for predicting outcome

Abstract Rationale: Early prognostication after out-of-hospital cardiac arrest (OHCA) is an unmet clinical need. There is limited data on serial release kinetics of cardiac, brain and systemic biomarkers such as Neuron Specific Enolase (NSE) and S-100B. miRNAs are sensitive biomarker candidates in acute myocardial infarction (MI). Objective The objective was to characterise circulating biomolecules in the early release kinetics after OHCA, compared with a STEMI control group and assessed with clinical outcome. Methods and Results Serial blood samples of patients with OHCA with STEMI (n=20) and STEMI control (n=20) were collected at baseline and at 6, 12, 24 and 48h after admission. Untargeted plasma proteomics were performed using data-independent acquisition–mass spectrometry (DIA–MS). Candidate proteins and miRNAs were quantified. Proteomics returned n=156 proteins with significantly different kinetics between OHCA and STEMI. Six clusters, depicting distinct biological pathways, with characteristic differences between OHCA and STEMI were identified. The most distinct and significant differences between OHCA and STEMI patients were seen for acute phase reactants LBP, AACT, CRP and the lipid metabolite A2GL as well as endothelial and platelet miR-126 and cardiomyocyte-apoptosis/ischemia-reperfusion related miR-320a. Cardiogenic shock was best characterised by differential kinetics of coagulation and complement related proteins FA9, HRG, FHR1 and inflammation related miR-146. The primary endpoint was poor neurological recovery at 30-days. Individuals with good outcome showed distinct differences in adaptive immune response, complement and coagulation cascades and hemostasis. Circulating plasma levels of hypoxia-associated miR-101, miR-210 and S-100B protein were significantly elevated at baseline in OHCA patients. These molecules further showed higher baseline values in patients with poor outcome. For current prognosis marker NSE, this difference only develops after 48h. Cardiac/muscle miRNAs followed an early release-pattern similar to high-sensitivity cardiac troponin-T (hs-cTnT). Machine learning models were used to calculate the AUC for the prediction of poor neurological outcome at baseline. This was highest for hypoxia-induced miR-210 (AUC: 0.854), which performed significantly better than the protein biomarkers NSE (AUC: 0.646) and S-100B (AUC:0.656). Conclusions Untargeted mass spectrometry reveals distinct biological pathways and candidate biomolecules affected in patients suffering from OHCA compared with STEMI controls, in patients developing cardiogenic shock and in those with adverse versus good neurological outcome. Platelet-, inflammation and hypoxia associated miRNAs are associated with OHCA, cardiogenic shock and prognostication of adverse neurological outcome. Pronounced differences in early release kinetics of RNA and protein biomarkers may improve identification of OHCA patients at risk of poor outcome.

Dysfunction of PTEN-Associated MicroRNA Regulation: Exploring Potential Pathological Links in Type 1 Diabetes Mellitus.

Background and Objectives: Type 1 Diabetes Mellitus (T1DM) is an autoimmune disease with T cell-mediated pathogenesis of pancreatic β-cell destruction, leading to insulin deficiency. MicroRNAs such as miR-223 and miR-106b, along with PTEN, have been reported to participate in the pathophysiology of diabetes and its complications. The current study has explored the expression of miR-223, miR-106b, and PTEN and their association with various clinical and biochemical parameters in subjects diagnosed with T1DM. Materials and Methods: Sixty T1DM patients (two groups as uncomplicated/ with microalbuminuria) and fifty healthy volunteers, age- and sex-matched, were enrolled in this study. The fasting venous blood samples were collected, and PTEN and miRNAs (miR-223 and miR-106b) levels were measured by ELISA and real-time PCR, respectively. Results: The PTEN levels of patients with microalbuminuria were significantly lower than those of patients without microalbuminuria, while those of miR-223 and miR-106b were significantly increased in the T1DM group compared with the healthy control group (p < 0.001). ROC analysis indicated that PTEN, miR-223, and miR-106b could be potential biomarkers for diagnosing T1DM with high specificity but with variable sensitivities. Also, PTEN and miR-223 were negatively correlated with r =-0.398 and p < 0.0001, indicating that they were interrelated in their role within the T1DM pathophysiology. Conclusions: In the current study, it has been shown that the circulating levels of PTEN, miR-223, and miR-106b are significantly changed in T1DM patients and may back their potential to be used as non-invasive biomarkers for the diagnosis and monitoring of T1DM. Low PTEN protein expression was related to high miR-223 expression, indicating involvement of these miRNA in the regulation of PTEN. Further studies should be performed to clarify the exact mechanisms and possible clinical applications of these molecules.

Quantitative detection of miR-25 for early diagnosis, postoperative assessment and TNM staging of pancreatic cancer

Objectives: Pancreatic cancer is one of the most common malignant tumors of the digestive tract. Due to its strong concealment and rapid disease progress, it is characterized by high mortality and low cure rate. Current research focuses on screening high-risk populations, preventing the occurrence of pancreatic cancer and developing imaging technology and tumor markers for early diagnosis. This study aimed to investigate the absolute quantitative detection of microRNA-25 (miR-25) and reveal its quantitative changes in the treatment of pancreatic cancer. We compared serum miR-25 level between pancreatic cancer patients and other tumor patients, especially those with gastrointestinal cancer, to provide further evidence for early diagnosis, differential diagnosis and prognosis of pancreatic cancer. Methods: We collected serum samples from 51 pancreatic cancer patients (including 21 patients with preoperative and postoperative samples), 52 pancreatitis patients, 141 other tumor patients, and 50 healthy individuals from Huashan Hospital, Fudan University. The serum levels of miR-25, Carbohydrate Antigen 19–9 (CA19–9), Carbohydrate Antigen 125 (CA125) and Carcinoembryonic Antigen (CEA) in these populations were measured to analyze the value of miR-25 quantitative detection in the diagnosis, postoperative assessment and Tumor Node Metastasis (TNM) staging of pancreatic cancer. Results: Among the 51 pancreatic cancer patients, 50 cases (98.04 %) showed miR-25 levels above the threshold (3333 copies/μl), while all samples in normal group showed negative. The mean level of miR-25 in serum was 5707.45 ± 361.02 copies/μl. In other tumor groups, 21/141 (14.89 %) patients showed positive results and the mean miR-25 level was 847.09 ± 125.97 copies/μl. Comparing before and after operation in 21 paired samples, the level of miR-25 declined significantly after operation, with an average decline rate of 86.36 %. Conclusions: Serum miR-25 levels were significantly higher in pancreatic cancer patients compared to both normal and other tumor groups and decreased significantly after surgery. In addition, miR-25 showed higher sensitivity than common tumor markers (CA19–9, CA125, CEA) in early diagnosis of pancreatic cancer, and proved to be of significant value in evaluating the effect of surgical treatment.

Extracellular vesicles and citrullination signatures are novel biomarkers in sturgeon (Acipenser gueldenstaedtii) during chronic stress due to seasonal temperature challenge

Acipenser gueldenstaedtii is one of the most cultured sturgeon species worldwide and of considerable economic value for caviar production. There are though considerable challenges around chronic stress responses due to increased summer temperatures, impacting sturgeons’ immune responses and their susceptibility to opportunistic infections. The identification of molecular and cellular pathways involved in stress responses may contribute to identifying novel biomarkers reflective of fish health status, crucial for successful sturgeon aquaculture. Protein citrullination is a calcium-catalysed post-translational modification caused by peptidylarginine deiminases (PADs), altering target protein function and affecting protein interactions in physiological and pathobiological processes. PADs can also modulate extracellular vesicle (EVs) profiles, which play critical roles in cellular communication, via transport of their cargoes (proteins, including post-translationally modified proteins, genetic material and micro-RNAs).This study identified differences in EV signatures, and citrullinated proteins in sera from winter and summer farmed sturegeons. EVs were significantly elevated in sera of the summer chronically stressed group. The citrullinated proteins and associated gene ontology (GO) pathways in sera and serum-EVs of chronically heat stressed A. gueldenstaedtii, showed some changes, with specific citrullinated serum protein targets including alpa-2-macroglobulin, alpha globin, calcium-dependent secretion activator, ceruloplasmin, chemokine XC receptor, complement C3 isoforms, complement C9, plectin, selenoprotein and vitellogenin. In serum-EVs, citrullinated protein cargoes identified only in the chronically stressed summer group included alpha-1-antiproteinase, apolipoprotein B-100, microtubule actin crosslinking factor and histone H3. Biological gene ontology (GO) pathways related to citrullinated serum proteins in the chronically stressed group were associated with innate and adaptive immune responses, stress responses and metabolic processes. In serum-EVs of the heat-stressed group the citrullinome associated with various metabolic GO pathways.In addition to modified citrullinated protein content, Serum-EVs from the stressed summer group showed significantly increased levels of the inflammatory associated miR-155 and the hypoxia-associated miR-210, but significantly reduced levels of the growth-associated miR-206.Our findings highlight roles for protein citrullination and EV signatures in response to chronic heat stress in A. gueldenstaedtii, indicating a trade-off in immunity versus growth and may be of value for sturgeon aquaculture.

The Involvement of miR-221/222 in Vascular Pathophysiology: Implications for Stenting.

MicroRNAs (miRNAs) are pivotal regulatory molecules involved in numerous cellular processes, including apoptosis, differentiation, proliferation, and migration. Recent research highlights specific miRNAs, such as the miR-221/222 cluster, which modulate key signaling pathways related to vascular smooth muscle cell (VSMC) proliferation, inflammation, and endothelial function. This function of miR-221/222 is accompanied by influencing the expression of certain proteins implicated in VSMCs and endothelial cells regulatory processes. miRNAs have been increasingly recognized for their roles in cardiovascular diseases, particularly in the mechanisms underlying in-stent restenosis and stent thrombosis. Elevated levels of miR-221/222 have been reported to be associated with severe adverse events following stenting and affect VSMC behavior and inflammatory responses. This image makes them promising candidates for new therapeutic strategies to address the most complex inferences of stenting, in-stent restenosis/stent thrombosis. Therefore, a discussion over the involvement of miR-221/222 in vascular pathophysiology could lead to finding possible signaling pathways and better stent designing for improving outcomes in patients undergoing stenting. Emerging therapeutic approaches, such as anti-miR oligonucleotides, offer the potential for translating these findings into clinical practice. This review article systematically investigates the biogenesis and functions of the miR-221/222 cluster along with its contributions to angiogenesis, vascular calcification, and neointimal formation. It aims to provide readers and researchers with insights into the signaling pathways that underpin vascular pathology linked to the miR-221 and miR-222 involvement.

Heparin-binding EGF-like growth factor via miR-126 controls tumor formation/growth and the proteolytic niche in murine models of colorectal and colitis-associated cancers

MicroRNAs, including the tumor-suppressor miR-126 and the oncogene miR-221, regulate tumor formation and growth in colitis-associated cancer (CAC) and colorectal cancer (CRC). This study explores the impact of the epithelial cytokine heparin-binding epidermal growth factor (HB-EGF) and its receptor epidermal growth factor receptor (EGFR) on the pathogenesis of CAC and CRC, particularly in the regulation of microRNA-driven tumor growth and protease expression. In murine models of CRC and CAC, lack of miR-126 and elevated miR-221 expression in colonic tissues enhanced tumor formation and growth. MiR-126 downregulation in colon cells established a pro-tumorigenic proteolytic niche by targeting HB-EGF-active metalloproteinase-7, -9 (MMP7/MMP9), disintegrin, and metalloproteinase domain-containing protein 9, and modulating chemokine-mediated recruitment of HB-EGF-loaded inflammatory cells. Mechanistically, downregulation of HB-EGF and EGFR in the colon suppressed miR-221 and enhanced miR-126 expression via activating enhancer-binding protein 2 alpha. Reintroducing miR-126 reduced tumor development and HB-EGF expression. Combining miR-126 reintroduction, which targets specific HB-EGF-active proteases but not ADAM17, with MMP inhibitors like Batimastat or Marimastat effectively suppressed tumor growth. This combination normalized protease expression and balanced miR-126 and miR-221 levels in developing and growing tumors. These findings demonstrate that suppressing HB-EGF and EGFR1 shifts the balance from oncogenic miR-221 to tumor-suppressive miR-126 action. Consequently, normalizing miR-126 expression could open new avenues for treating patients with CAC and CRC, and this normalization is intertwined with the anticancer efficacy of MMP inhibitors.

LncRNA LYPLAL1, miR-204-5p, and SIRT1: novel signatures for risk assessment of diabetic macrovascular complications

Long-term, uncontrolled diabetes mellitus can lead to micro- and macrovascular problems. The protective function of lncRNA LYPLAL1 is to reduce endothelium cell inflammation by upregulating sirtuin 1 (SIRT1) and reducing microRNA (miR)-204-5p. This work attempted to examine the lncRNA LYPLAL1/miR-204-5p/SIRT1 molecules as diagnostic biomarkers for diabetic MVC and to assess their clinical correlations. The study enrolled 32 controls, 32 patients with diabetes alone, and 32 patients with diabetic MVC. RT-qPCR, or quantitative real-time PCR, was utilized to determine the expression levels of lncRNA and miR. SIRT1 was measured by ELISA. When comparing cases with MVC to those without MVC, the lncRNA LYPLAL1 and SIRT1 values were significantly lower. Conversely, patients with MVC had significantly higher miR-204-5p levels than those without MVC. The LncRNA LYPLAL1 performed best in terms of detecting MVC. It attained 90.6% specificity and 96.9% sensitivity. A combination of three markers (lncRNA LYPLAL1, miR-204-5p, and SIRT1) yielded the best accuracy at 98.4%. LYPLAL1 expression appeared to be an independent MVC predictor. Adjusted OR for LYPLAL1 expression was 405 (95% CI: 1.4–1200) (p = 0.039). When we compared cases with MVC to those without MVC, the lncRNA LYPLAL1 and SIRT1 values were significantly lower. Patients with MVC had significantly higher miR-204-5p levels than those without MVC. LYPLAL1 LncRNA demonstrated the best performance characteristics. LncRNA LYPLAL1 expression is an independent predictor of MVC.

Different expression patterns of inflammation-related genes and serum microRNAs in young-onset ischemic stroke

Brain ischemia results in the activation of a cascade of inflammatory responses, contributing to the pathogenesis of stroke. This study aimed to assess the patterns of possible changes in the expression of specific inflammation-associated protein-encoding genes and miRNAs in the peripheral blood between the acute and chronic phase of young-onset cryptogenic (Cryp) and large-artery atherosclerotic (LAA) stroke. Blood and serum were collected from patients with cryptogenic and large-artery atherosclerotic stroke at the stroke onset and 1-year follow-up. The relative expression of inflammation-related genes was analysed at the mRNA and miRNA levels using real-time quantitative PCR. Moreover, the relationship between the relative gene expression levels and clinical data was assessed using several different statistical approaches. Seventy-three patients were included in this study, with a median age of 47 (IQR, 9) years. Approximately 72% were men. In patients with cryptogenic stroke, at the mRNA level, ICAM1, CXCL8, TNF, NFKBIA, PYCARD, IL1B, and IL18 were observed to be upregulated at the stroke onset compared to the 1-year follow-up. In patients with LAA stroke, only the expression of NFKBIA was significantly higher during acute stroke. Further, the miRNA serum levels of miR-21, miR-122, and miR-155 were higher at the onset of stroke in patients with cryptogenic stroke but not in those with LAA stroke. The differences between the relative gene expression levels during acute stroke and at the 1-year follow-up were more pronounced in patients with cryptogenic stroke with no cardiovascular risk factors. The expression changes of inflammatory genes in whole blood and miRNAs in the serum differ in patients with cryptogenic and LAA stroke.

CLINICAL SIGNIFICANCE OF SALIVARY MIR-21, -155, AND -375 IN PATIENTS WITH SQUAMOUS CELL CARCINOMA OF ORAL CAVITY.

The current prognostic markers in oral squamous cell carcinoma (OSCC) have limited accuracy sometimes leading to inappropriate treatment decisions. Identifying new markers would help clinicians tailor treatment plans based on the individual patient risk factors leading to improved survival rates and quality of life. To estimate the value of the miRNA expression indicators in saliva as prognostic and predictive markers of the effectiveness of neoadjuvant chemotherapy (NACT). The work is based on the results of the examination and treatment of 61 patients with stage II-IV OSCC. The miR-21, miR-155, and miR-375 expression levels in the saliva samples were analyzed by the real-time reverse transcription polymerase chain reaction. The salivary miR-21 and -155 expression levels in healthy volunteers were 2.49 and 2.84 times lower than in OSCС patients (p < 0.05). The positive association of miR-21 and miR-155 expression levels and the negative correlation of miR-375 expression level with T index by TNM (r = 0.68, r = 0.75, and r = -0.67, respectively) (p < 0.05) and the presence of lymph node metastasis (r = 0.78, r = 0.71, and r = ‒0.59, respectively) (p < 0.05) were found. Patients with good response to NACT had lower miR-21 and -155, and higher miR-375 levels in saliva compared to those with resistant tumors. Our study suggests that salivary miR-21, miR-155, and miR-375 may be potential biomarkers for the prognosis of cancer course and the response to NACT in OSCC patients.

Genetic Signature of a Healthy Lifestyle: New Horizons for Preventing Noncommunicable Chronic Diseases by Modulating MicroRNA-155.

The development and progression of several noncommunicable diseases (NCDs) are associated with microRNA (miR) 155 (miR-155) activation, which promotes inflammation and oxidative stress. In particular, miR-155 regulates nuclear transcription factor-kappa B (NF-κB) by silencing gene expression of proteins involved in NF-κB suppression, such as suppressor of cytokine signaling 1 (SOCS1) and SH-2 containing inositol 5' polyphosphate 1 (SHIP1), increases the production of reactive oxygen species, and suppresses gene expression of antioxidant enzymes through nuclear factor erythroid 2-related factor 2 (Nrf2) inhibition. In this context, a healthy lifestyle based on a diet rich in nutrients and bioactive compounds as well as regular physical activity may modulate the activity of several miRs. Following this concept, studies involving nutrients, bioactive compounds, and physical activity have been developed to modulate miR-155 activation. This narrative review aims to discuss how a healthy lifestyle based on a diet rich in nutrients, bioactive compounds, and physical activity may modulate the miR-155 pathway and consequently prevent the development and progression of NCDs. Nutrients and bioactive compounds from food may act by inhibiting pathways that promote miR-155 activation such as NF-κB and promote activation of pathways that are associated with the downregulation of miR-155, such as Nrf2, and SOCS1 pathways. Regular physical activity also seems to influence miR-155 levels through an improvement in the immune system during muscle recovery. There is relevant evidence that shows a positive effect of nutrients, bioactive compounds, and physical activity with the modulation of miR-155, which can potentially provide benefits in the clinical setting in cases of NCDs.

Endometriotic lesions and their recurrence: A Study on the mediators of immunoregulatory (TGF-β/miR-20a) and stemness (NANOG/miR-145)

Endometriosis is a common estrogen-dependent disease that involves various cellular processes. Additionally, miRNAs play a crucial role in the development of the disease as an important component of the microenvironment. In this study, tissue specimens of eutopic and ectopic lesions of 20 women, whose endometriosis was later approved by the pathology laboratory, were biopsied through laparoscopy. As a control group, endometrial tissue specimens were collected from 20 women who underwent curettage for reasons unrelated to endometriosis. The expression levels of miR-20A and miR-145 and their target genes, TGF-β and NANOG, were measured in these samples as markers of stemness and immunomodulatory properties, respectively. The study also aimed to compare the expression levels of target genes and miRNAs in ectopic lesions regarding endometriosis recurrence post-surgery. The study revealed that the expression of TGF-β and NANOG genes was significantly upregulated in endometriotic tissues compared to the control group. There was also a notable increase in miR-20A and miR-145 expression in the endometriotic tissues compared to the control group. While there was no significant correlation between the expression of miR-20a and TGF-β, we observed a negative correlation between the expression level of miR-145 and NANOG. Additionally, the ROC curve analysis emphasized miR-14 as a potential biomarker for endometriosis over miR-20a. However, our findings on disease recurrence underscore the importance of miR-20a in the early detection of endometriosis recurrence.