miR-21 Expression Research Articles

The Multifaceted Roles of MicroRNA-181 in Stem Cell Differentiation and Cancer Stem Cell Plasticity

Stem cells are undifferentiated or partially differentiated cells with an extraordinary ability to self-renew and differentiate into various cell types during growth and development. The epithelial–mesenchymal transition (EMT), a critical developmental process, enhances stem cell-like properties in cells, and is associated with both normal stem cell function and the formation of cancer stem cells. Cell stemness and the EMT often coexist and are interconnected in various contexts. Cancer stem cells are a critical tumor cell population that drives tumorigenesis, cancer progression, drug resistance, and metastasis. Stem cell differentiation and the generation of cancer stem cells are regulated by numerous molecules, including microRNAs (miRNAs). These miRNAs, particularly through the modulation of EMT-associated factors, play major roles in controlling the stemness of cancer stem cells. This review presents an up-to-date summary of the regulatory roles of miR-181 in human stem cell differentiation and cancer cell stemness. We outline studies from the current literature and summarize the miR-181-controlled signaling pathways responsible for driving human stem cell differentiation or the emergence of cancer stem cells. Given its critical role in regulating cell stemness, miR-181 is a promising target for influencing human cell fate. Modulation of miR-181 expression has been found to be altered in cancer stem cells’ biological behaviors and to significantly improve cancer treatment outcomes. Additionally, we discuss challenges in miRNA-based therapies and targeted delivery with nanotechnology-based systems.

MIR-155 as a potential biomarker for disease severity in st-segment elevation myocardial infarction: insights from a university-affiliated cardiovascular center.

MiR-155 plays a role in inflammatory pathways and cardiovascular diseases, though its relationship with inflammation, atherosclerosis, and outcomes in ST-elevation myocardial infarction (STEMI) is not well established. To investigate associations between miR-155 levels, inflammation, atherosclerotic burden, and major adverse cardiovascular events (MACE) in STEMI patients. Sixty-nine STEMI patients and 16 healthy controls were recruited from a specialized university-affiliated cardiovascular center. MiR-155 expression and serum interleukin (IL)-1β, IL-6, and tumor necrosis factor levels were measured. Patients were grouped into tertiles based on miR-155 expression. Clinical data, atherosclerotic burden (through cardiac catheterization), and in-hospital MACE were recorded. MiR-155 levels were significantly lower in STEMI patients compared to controls (median 54.2, vs. 152.8 arbitrary units; p = 0.003). Higher miR-155 tertiles were associated with a greater prevalence of three-vessel occlusion (34% vs. 13% vs. 4%; p = 0.007) and increased incidence of pulmonary edema (13% vs. 0% vs. 0%; p = 0.030). No significant correlation was found between miR-155 and inflammatory or myocardial markers. Dysregulated miR-155 expression in STEMI patients may influence disease severity and MACE risk, independent of inflammation or myocardial damage markers.

MiRNAs and tempol therapeutic potential in prostate cancer: a preclinical approach.

This study investigated tempol action on genes and miRNAs related to NFκB pathway in androgen dependent or independent cell lines and in TRAMP model in the early and late-stages of cancer progression. A bioinformatic search was conducted to select the miRNAs to be measured based on the genes of interest from NFκB pathway. The miR-let-7c-5p, miR-26a-5p and miR-155-5p and five target genes (BCL2, BCL2L1, RELA, TNF, PTGS2) were chosen for RT-PCR and gene enrichment analyses. In vitro, PC-3 and LNCaP cells were exposed, respectively, to 1.0 or 2.0 mM of tempol during 48h. In vivo, five experimental groups were evaluated regarding tempol effects in the early (CT12 and TPL12 groups) and late-stages (CT20, TPL20-I and TLP20-II) of PCa development. TPL groups were treated with 50mg/kg or 100mg/kg of tempol. The ventral lobe of the prostate and the plasma was collected. Tempol treatment increased miRs expression in PC-3 and LNCaP. For both cell lines, tempol decreased RELA expression. In TRAMP model, tempol increased miRNA expression in prostate for all treated groups. Tempol upregulated the miRNA expressions related to the NFκB pathway in the prostate tissue and human tumor cell lines. Their increase is mainly linked to increased cell death and delayed CaP aggressivenes. Thus, tempol's capacity for miRNA-mediated gene silencing to decrease tissue proliferation and cell survival processes is part of its tissue mechanics.

New insights into the interplay between MALAT1 and miRNA-155 to unravel potential diagnostic and prognostic biomarkers of Behçet's disease.

The current study was deployed to evaluate the role of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and miR-155, along with the inflammatory markers, TNFα and IL-6, and the adhesion molecule, cluster of differentiation 106 (CD106), in Behçet's disease (BD) pathogenesis. The study also assessed MALAT1/miR-155 as promising diagnostic and prognostic biomarkers for BD. The current retrospective case-control study included 74 Egyptian BD patients and 50 age and sex-matched controls. Blood samples were collected, and then, serum samples were separated for further biochemical and molecular investigations. The gene expression of MALAT1 and miR-155 was measured using qRT-PCR, whereas the levels of TNFα, IL-6, and CD106 were estimated using ELISA technique. MALAT1 was significantly downregulated, whereas miR-155 was upregulated among BD patients, compared with control subjects. Levels of TNFα, IL-6, and CD106 were elevated in BD patients. Further downregulation in MALAT1 together with upregulation of miR-155 was observed in active BD patients, relative to the inactive group. Receiver-operating-characteristic analysis revealed that MALAT1 and miR-155 could discriminate BD patients from controls, on the one hand, and active from inactive BD patients, on the other hand. MALAT1 was negatively correlated with TNFα, IL-6, and CD106, while miR-155 was positively correlated with them. Logistic regression analyses demonstrated miR-155 as a significant independent predictor of BD susceptibility, and MALAT1 as an independent negative predictor of BD activity. For the first time, the current research enlightens the role of MALAT1 and miR-155 in BD pathogenesis via impacting IL-6/TNF-α/CD-106 signaling. As well, MALAT1 and miR-155 could be regarded as novel non-invasive biomarkers that may improve BD diagnosis and prognosis. Key Points •MALAT1/miR-155 exerts potential role in Behçet's disease. •MALAT1/miR-155 are promising biomarkers for Behçet's disease. •MALAT1/miR-155 targets IL-6/TNF-α/CD-106 signaling.

Changes in Levels of MiR-21, MiR-27a, MiR-221, and MiR-429 in the Thymus after Photodynamic Therapy and Surgical Treatment of Breast Cancer in Female Wistar Rats.

We studied the expression levels of microRNAs (miR-21, miR-27a, miR-221, and miR-429) in the thymus of female Wistar rats after surgical treatment of breast cancer (BC) and after photodynamic therapy for BC followed by tumor resection. In the group without treatment, the levels of pro-oncogenic miR-21, miR-27a, and miR-221 in the thymus were reduced in comparison with those in the group of intact control. After surgical treatment of BC, the levels of miR-21 and miR-27a in the thymus increased in comparison with those in BC without treatment. Surgical removal of the tumor followed by photodynamic therapy led to an even greater increase in the levels of miR-21 and miR-27a in the thymus in comparison with those in the group of surgical treatment alone. Expression of the tumor-suppressive miR-429 in the thymus significantly exceeds the levels in the BC without treatment and BC+surgery groups.

Agathisflavone Inhibits Viability and Modulates the Expression of miR-125b, miR-155, IL-6, and Arginase in Glioblastoma Cells and Microglia/Macrophage Activation.

Glioblastomas (GBM) are malignant tumours with poor prognosis. Treatment involves chemotherapy and/or radiotherapy; however, there is currently no standard treatment for recurrence, and prognosis remains unfavourable. Inflammatory mediators and microRNAs (miRNAs) influence the aggressiveness of GBM, being involved in the communication with the cells of the tumour parenchyma, including microglia/macrophages, and maintaining an immunosuppressive microenvironment. Hence, the modulation of miRNAs and inflammatory factors may improve GBM treatments. In this study, we investigated the effects of agathisflavone, a biflavonoid purified from Cenostigma pyramidale (Tul.), on the growth and migration of GBM cells, on the expression of inflammatory cytokines and microRNAs, as well on the response of microglia. Agathisflavone (5-30 μM) induced a dose- and time-dependent reduction in the viability of both human GL-15 and rat C6 cells, as determined by the MTT test, and reduced cell migration, as determined by cell scratch assay. RT-qPCR analysis revealed that agathisflavone (5 μM) down-regulated the expression of miR-125b and miR-155 in the secretome derived from GL-15 cells, which was associated with upregulation of the mRNA expression of IL-6 and arginase-1 immunoregulatory factors. Exposure of human microglia/macrophage to the secretome from GL-15 GMB cells modulated proliferation and morphology, effects that were modulated by agathisflavone treatment. These results demonstrate the effect of flavonoids on the growth of GBM cells, which impacts cells in the microenvironment and can be considered for preclinical studies for adjuvant treatments.

Identification of the EBF1/ETS2/KLF2-miR-126-Gene Feed-Forward Loop in Breast Carcinogenesis and Stemness.

MicroRNA (miR)-126 is frequently downregulated in malignancies, including breast cancer (BC). Despite its tumor-suppressive role, the mechanisms underlying miR-126 deregulation in BC remain elusive. Through silencing experiments, we identified Early B Cell Factor 1 (EBF1), ETS Proto-Oncogene 2 (ETS2), and Krüppel-Like Factor 2 (KLF2) as pivotal regulators of miR-126 expression. These transcription factors were found to be downregulated in BC due to epigenetic silencing or a "poised but not transcribed" promoter state, impairing miR-126 expression. Gene Ontology analysis of differentially expressed miR-126 target genes in the Cancer Genome Atlas: Breast Invasive Carcinoma (TCGA-BRCA) cohort revealed their involvement in cancer-related pathways, primarily signal transduction, chromatin remodeling/transcription, and differentiation/development. Furthermore, we defined interconnections among transcription factors, miR-126, and target genes, identifying a potential feed-forward loop (FFL) crucial in maintaining cellular identity and preventing the acquisition of stemness properties associated with cancer progression. Our findings propose that the dysregulation of the EBF1/ETS2/KLF2/miR-126 axis disrupts this FFL, promoting oncogenic transformation and progression in BC. This study provides new insights into the molecular mechanisms of miR-126 downregulation in BC and highlights potential targets for therapeutic intervention. Further research is warranted to clarify the role of this FFL in BC, and to identify novel therapeutic strategies aimed at modulating this network as a whole, rather than targeting individual signals, for cancer management.

Association of MicroRNA-103 expression with type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM), the most prevalent metabolic disorder worldwide, has genetic, epigenetic, and environmental contributors. Among them, circulating microRNAs (miRNAs/miRs) have attracted considerable attention. This study aimed to investigate the regulatory role of miR-103 in T2DM development. The miR-103 expression was evaluated in 33 participants with T2DM compared with 38 healthy controls using quantitative real-time polymerase chain reaction (q-RT PCR). Fasting blood glucose (FBS), fasting insulin (Fin), hemoglobin A1c (HbA1c), triglycerides (TG), and cholesterol (Chol) were also determined in serum. Basal insulin resistance and sensitivity were determined using the homeostasis model assessment insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI), respectively. There was a significant decrease in miR-103 levels in patients with T2DM (p<0.002). Serum miR-103 expression levels showed a strong correlation with age, FBS, HbA1c, TG, Chol levels, and HOMA-IR and QUICKI indices. The downregulation of miR-103 in T2DM patients suggests the diagnostic potential of miR-103 evaluation in conjunction with other diagnostic approaches.

Role of Decreased Expression of miR-155 and miR-146a in Peripheral Blood of Type 2 Diabetes Mellitus Patients with Diabetic Peripheral Neuropathy [Letter

Role of Decreased Expression of miR-155 and miR-146a in Peripheral Blood of Type 2 Diabetes Mellitus Patients with Diabetic Peripheral Neuropathy [Letter

Association of circulating Treg and plasma microRNA-21 with rheumatoid arthritis progression

The etiology of rheumatoid arthritis (RA) is multifaceted. One of the hypothesized pathways that results in the progression of RA is regulatory T cell (Treg) dysfunction. The pro-osteoclastogenic and immunogenic characteristics of microribonucleic acid (microRNA)-21 (miR-21) suggest its role in RA progression. Hence, we investigated the significance of plasma miR-21 and Treg cell frequency as biomarkers for RA progression and assessed the link between miR-21 and Treg frequency in RA. This study enrolled 60 RA patients classified according to disease activity score 28-joint count with erythrocyte sediment rate (DAS28-ESR) to inactive cases (n = 30) and active cases (n = 30). Flow cytometer was used to assess Treg frequency. The Real-time quantitative PCR was used to measure the expression levels of miR-21 in plasma. When compared to the inactive group, the active group revealed significant up-regulation of miR-21 expression (p = 0.004) and down-regulation of Treg frequency (p&lt;0.001). While Treg frequency was negatively correlated, miR-21 fold change was positively correlated with DAS-28-ESR (r = -508, p &lt; 0.001 and r = 0.334, p &lt; 0.009, respectively). No correlation was detected between mirR-21 and Treg frequency. Treg distinguished the two groups at area under the curve (AUC) of 0.907 with 86.7% sensitivity and 73.3% specificity, whereas miR-21 up-regulation discriminated active from inactive RA patients at AUC of 0.717, with 83.3% sensitivity and 53.3% specificity. In conclusion, Treg frequency and miR-21 fold were differentially linked to DAS-28-ESR in RA. MiR-21 fold up-regulation changes and Treg frequency down-regulation can be suggested as biomarkers for RA activity.

Comparative analysis of fennel essential oil and manganese in PCOS rat model via modulating miR-145 expression and structure-based virtual screening of IGF2R protein to address insulin resistance and obesity

Comparative analysis of fennel essential oil and manganese in PCOS rat model via modulating miR-145 expression and structure-based virtual screening of IGF2R protein to address insulin resistance and obesity

Differential Expression of miR-192, miR-221, miR-15 Among the Nodule Tissues of Sarcoidosis and Lung Cancer

Background: Patients with sarcoidosis were found to have a higher risk of lung cancer compared to the general population. Being aware of all possible associations between these two diseases and identification of biomarkers such as miRNA profiles can be helpful in differentiating the mechanisms of these two diseases, which can aid in clinical decision-making. Methods: The aim of the study was to investigate the expression of selected miRNAs (miR-192 miR-221, miR-15) in lymph nodes of patients with pulmonary sarcoidosis, non-small cell lung carcinomas (NSCLC) and control group (n = 30 per groups) by qRT-PCR. Results: Relative expression of miR-221 in sarcoidosis and NSCC patients was higher than in the control group. Furthermore, the relative expression of miR-15 in patients with sarcoidosis and NSCLC tissue was lower than in the control group. Interestingly, miR-192 is differentially expressed in sarcoidosis and NSCLC patients compared to the control group. Conclusions: The obtained results suggest that the studied miRNAs may have potential diagnostic and therapeutic implications, but further research is necessary to fully understand their roles in these diseases.

Impact of cataranthine treatment on miRNA34 and miRNA29 levels in HepG2 cells and their association with the expression levels of Bcl-2 and Nrf2.

Cataranthine is an alkaloid used in the development of anti-cancer drugs. In this study, the effect of cataranthine is assessed by measuring the levels of miR-34 and miRNA-29, which are effective regulators of BCL-2 and NRF-2 gene expression, and their relation to the survival of HCC cells. This study used cataranthine, and the HepG2 cell line. The MTT test was used to determine the appropriate concentration of cataranthine for treatment (IC50). Oxidative stress status was assessed by evaluating TAC (total antioxidant capacity), TOS (total oxidant status), and MAD (malondialdehyde) levels. Flow cytometry was used to investigate apoptosis. The expression levels of Nrf2, Bcl2, miRNA34, and miRNA29 genes in HepG2 were evaluated by RT-PCR. We observed that cataranthine significantly reduced the levels of oxidative markers (MAD, and TOS) and, conversely, increased the level of antioxidant markers in HepG2 cells. Treatment of HepG2 cells with different doses of cataranthine significantly increased the expression of Nrf2 and Bcl-2 genes, while significantly decreasing the expression of miR29 and miR34 genes. These findings suggest that cataranthine may exert its anticancer effects by reducing oxidative stress and promoting apoptosis, while decrease in miR34 and miR29 as well as increase in Nrf2 and Bcl2 may act as resistance mechanisms in cancer cells. The results highlight the dual potential of cataranthine in regulating cellular responses to oxidative stress and cell death in liver cancer, with dose-dependent modulatory effects.

Evaluation of Plasma microRNA-222 as a Biomarker for Gastric Cancer.

Background: The dysregulation of microRNAs (miRNAs) has been detected in patients with gastric cancer (GC), which inspired the use of miRNAs as a novel biomarker for GC. In this study, we investigated the previously reported miRNA dysfunction in cancer tissues as a potential plasma biomarker for GC using quantitative reverse transcriptase polymerase chain reaction (RT-PCR). Methods: The published miRNA abnormalities were searched in the microRNA Cancer Association Database. Plasma samples were collected from patients with GC (n = 26) and controls (n = 17). The sensitivity and specificity of polyadenylation RT-PCR (PA-RT) and stem-loop RT-PCR (SL-RT) were compared. Statistical comparisons between patients with GC and controls were performed to identify miRNA biomarkers, and correlation analyses between the threshold cycle (Ct) values of miRNAs and various blood biochemical parameters were performed to elucidate the confounding factors. Results: mir-17, mir-21, mir-31, mir-99b, mir-222, and U6 were selected. PA-RT showed greater sensitivity and lower specificity than SL-RT (PA-RT vs. SL-RT, mean Ct: 19.6 vs. 29.2; coefficient of variation: 0.42 vs. 0.10). Adopting SL-RT owing to its higher specificity, only mir-222 was significantly upregulated in patients with GC (GC vs. control, miRNA expression: 15.4 vs. 5.27, p = 0.0098). Regarding the correlation between blood biochemical parameters and cells with miRNA expression, mir-31 and mir-99b were correlated with blood urea nitrogen, mir-17, mir-21, and mir-99b were negatively correlated with platelets, and mir-21 was correlated with neutrophils. No obvious correlations were noted between mir-222 expression and blood parameters. Receiver operating characteristic (ROC) curve analysis indicated that mir-222 identified GC patients with a maximum area under the curve (0.73, 95% confidence interval 0.57-0.89). Conclusions: Plasma mir-222 was confirmed to be dysregulated in patients with GC, irrespective of blood biochemical parameters.

Hypoxia Regulates Brown Adipocyte Differentiation and Stimulates miR-210 by HIF-1α.

MicroRNAs (miRNAs) are short sequences of single-stranded non-coding RNAs that target messenger RNAs, leading to their repression or decay. Interestingly, miRNAs play a role in the cellular response to low oxygen levels, known as hypoxia, which is associated with reactive oxygen species and oxidative stress. However, the physiological implications of hypoxia-induced miRNAs ("hypoxamiRs") remain largely unclear. Here, we investigate the role of miR-210 in brown adipocyte differentiation and thermogenesis. We treated the cells under sympathetic stimulation with hypoxia, CoCl2, or IOX2. To manipulate miR-210, we performed reverse transfection with antagomiRs. Adipocyte markers expression, lipid accumulation, lipolysis, and oxygen consumption were measured. Hypoxia hindered BAT differentiation and suppressed sympathetic stimulation. Hypoxia-induced HIF-1α stabilization increased miR-210 in brown adipocytes. Interestingly, miR-210-5p enhanced differentiation under normoxic conditions but was insufficient to rescue the inhibition of brown adipocyte differentiation under hypoxic conditions. Although adrenergic stimulation activated HIF-1α signaling and upregulated miR-210 expression, inhibition of miR-210-5p did not significantly influence UCP1 expression or oxygen consumption. In summary, hypoxia and adrenergic stimulation upregulated miR-210, which impacted brown adipocyte differentiation and thermogenesis. These findings offer new insights for the physiological role of hypoxamiRs in brown adipose tissue, which could aid in understanding oxidative stress and treatment of metabolic disorders.

Circulating MiR-126 as a potential biomarker in Egyptian colorectal cancer patients: A case-control study.

Globally, colorectal cancer (CRC) is among the most prevalent malignant tumors. It is characterized by unlimited proliferation, invasion, and metastasis. MicroRNA-126 (miR-126) has been shown in many studies to play a significant role in CRC, but data regarding its role in CRC Egyptian patients are limited. This case-control study aimed to investigate the miR-126 as a potential marker in CRC Egyptian patients and to correlate its expression levels with CRC tumor, node, metastasis (TNM) stage, distant metastasis, and tumor size. The study included 50 adult Egyptian participants (30 patients with CRC, 10 patients with colorectal adenoma as a pathological control, and 10 healthy controls). MiR-126 expression levels were detected using Real-Time Quantitative PCR (qPCR) along with the endogenous reference gene hsa-miR-103a in all participants. MiR-126 expression was significantly decreased in CRC patients than both control groups. It was associated with advanced TNM stage (p = 0.001) and distant metastasis (p = 0.002). However, it was not correlated with tumor size (p = 0.980), carcinoembryonic antigen (CEA) (p = 0.397), and cancer antigen 19-9 (CA19-9) (p = 0.236). The best cut-off point of miR-126 to discriminate CRC from both controls was 0.7 and to discriminate metastatic CRC from non-metastatic CRC was 0.3. Our results suggest that miR-126 could be used as an early marker for CRC detection among Egyptian patients and a good prognostic indicator associated with metastasis.

Click chemistry-based dual nanosystem for microRNA-122 detection with single-base specificity from tumour cells

MicroRNAs (miRNAs) have been recognised as potential biomarkers due to their specific expression patterns in different biological tissues and their changes in expression under pathological conditions. MicroRNA-122 (miR-122) is a vertebrate-specific miRNA that is predominantly expressed in the liver and plays an important role in liver metabolism and development. Dysregulation of miR-122 expression is associated with several liver-related diseases, including hepatocellular carcinoma and drug-induced liver injury (DILI). Given the potential of miR-122 as a biomarker, its effective detection is important for accurate diagnosis. However, miRNA detection methods still face challenges, particularly in terms of accurately identifying miRNA isoforms that may differ by only a single base. Here, with the aim of advancing accessible methods for the detection of miRNAs with single-base specificity, we have developed a robust dual nanosystem that leverages the simplicity of click chemistry reactions. Using the dual nanosystem, we successfully detected miR-122 at single-base resolution using flow cytometry and analysed its expression in various tumour cell lines with high specificity and strong correlation with TaqMan assay results. We also detected miR-122 in serum and identified four single nucleotide variations in its sequence. The chemistry employed in this dual nanosystem is highly versatile and offers a promising opportunity to develop nanoparticle-based strategies that incorporate click chemistry and bioorthogonal chemistry for the detection of miRNAs and their isoforms.Graphical

MicroRNA-150 Deletion from Adult Myofibroblasts Augments Maladaptive Cardiac Remodeling Following Chronic Myocardial Infarction.

MicroRNA (miR: small noncoding RNA)-150 is evolutionarily conserved and is downregulated in patients with diverse forms of heart failure (HF) and in multiple mouse models of HF. Moreover, miR-150 is markedly correlated with the outcome of patients with HF. We previously reported that systemic or cardiomyocyte-derived miR-150 in mice elicited myocardial protection through the inhibition of cardiomyocyte death, without affecting neovascularization and T cell infiltration. Our mechanistic studies also showed that the protective roles of miR-150 in ischemic mouse hearts and human cardiac fibroblasts were, in part, attributed to the inhibition of fibroblast activation via the repression of multiple profibrotic genes. However, the extent to which miR-150 expression in adult myofibroblasts (MFs) modulates the response to myocardial infarction (MI) remains unknown. Here, we develop a novel 4-hydroxytamoxifen-inducible MF-specific miR-150 conditional knockout mouse model and demonstrate that the mouse line exhibits worse cardiac dysfunction after MI. Our studies further reveal that miR-150 ablation selectively in adult MFs exacerbates cardiac damage and apoptosis after chronic MI. Lastly, MF-specific miR-150 deletion in adult mice promotes the expression of proinflammatory and profibrotic genes as well as cardiac fibrosis following chronic MI. Our findings indicate a key protective role for MF-derived miR-150 in modulating post-MI responses.

Elevated miRNA-499 Levels in Early Phase of Non-ST Elevation Acute Coronary Syndromes Predict Increased Long-Term Risk of Major Adverse Cardiac Events.

Background/Objectives: Available data suggest the diagnostic potential of testing microRNAs (miRs) in myocardial infarction, but their prognostic value remains unclear. To evaluate the prognostic value of circulating miRs (miR-1, miR-21, miR-133a, miR-208 and miR-499) for predicting major adverse cardiac events (MACEs), including death, non-fatal myocardial infarction (MI) or cardiovascular rehospitalization, in patients with non-ST segment elevation acute coronary syndromes (NSTE-ACS). Methods: Our prospective, single-center, observational study included patients (pts) with NSTE-ACS admitted <24 h after symptoms onset and pts with confirmed stable coronary artery disease (SCAD) as controls. Relative expression of miRs was calculated, and subjects were categorized according to miRs expression on hospital admission into two groups (≤median and >median). Results: Overall, 103 NSTE-ACS (52 NSTEMI/51 UA) and 47 SCAD pts (median age 66 years, 67% male) were included. During the median 895 (581-1134) days of the follow-up, MACE occurred in 75 (50%) patients: 20 (13%) died, 28 (19%) presented with MI, and 65 (43%) were readmitted due to cardiovascular reasons. Incidence of MI, rehospitalization and MACE was significantly higher in pts with elevated (>median) miR-499 [MI: 34.3% vs. 7.3%; HR = 6.0 (2.8-12.7) for rehospitalization; 53.7% vs. 36.2%, HR = 2.3 (1.4-3.8) for MACE; 62.7% vs. 42%, HR = 2.4 (1.5-3.8)] for hospital readmission. In the Cox proportional hazards regression model, miR-499 expression above the median level [HR = 1.8 (1.1-3.1)], high-sensitivity cardiac troponin T [HR = 1.2 (1.02-1.5)], diabetes [HR = 1.7 (1.1-2.8)] and percutaneous intervention during hospital stay [HR = 2.1 (1.1-3.8)] were identified as independent predictors of MACE in long-term observation, even after adjustment for covariates. Conclusions: Elevated miR-499 level on hospital admission in NSTE-ACS is related to an increased rate of MACE in the 2.5-year follow-up.

The diagnostic and predictive potential of lncRNA CASC2 targeting miR-155 in systemic lupus erythematosus patients with nephritis complication

Lupus nephritis (LN) is a serious problem that results from systemic lupus erythematosus (SLE) complications. Recent studies have highlighted that non-coding RNA (ncRNA) dysregulation is a notable feature in patients with SLE. As a result, this research was designed to investigate lncRNA CASC2 and miR-155 levels as non-invasive diagnostic biomarkers in SLE patients, including those with and without nephritis, and to investigate their effectiveness in assessing disease severity and predicting LN. Our study included 60 patients with SLE who were subclassified into (30 non-LN and 30 LN groups), along with 30 control subjects. Quantification of lncRNA CASC2 and miR-155 in serum samples from the Egyptian population was carried out with real-time polymerase chain reaction (RT-PCR). The disease activity index (SLEDAI) for SLE was evaluated, and the analysis of the receiver operating characteristic (ROC) curve was implemented. Increased levels of lncRNA CASC2 were observed in SLE patients compared to healthy controls, with even higher levels observed in the LN group versus the non-LN patients’ group. Conversely, miR-155 was noted to be down-regulated in SLE patients relative to controls, and its levels were lower in the LN group relative to the non-LN patients’ group. The elevated expression of lncRNA CASC2 and reduced expression of miR-155 were both correlated to the severity of the disease. The current study illustrated that both lncRNA CASC2 and miR-155 could act as valuable non-invasive diagnostic biomarkers for SLE and predicting LN among SLE patients, as well as their abilities to detect the disease severity and progression.