miR-21 Expression Research Articles

AAV-Mediated Expression of miR-17 Enhances Neurite and Axon Regeneration In Vitro.

Neurodegenerative disorders, including traumatic injuries to the central nervous system (CNS) and neurodegenerative diseases, are characterized by early axonal damage, which does not regenerate in the adult mammalian CNS, leading to permanent neurological deficits. One of the primary causes of the loss of regenerative ability is thought to be a developmental decline in neurons' intrinsic capability for axon growth. Different molecules are involved in the developmental loss of the ability for axon regeneration, including many transcription factors. However, the function of microRNAs (miRNAs), which are also modulators of gene expression, in axon re-growth is still unclear. Among the various miRNAs recently identified with roles in the CNS, miR-17, which is highly expressed during early development, emerges as a promising target to promote axon regeneration. Here, we used adeno-associated viral (AAV) vectors to overexpress miR-17 (AAV.miR-17) in primary cortical neurons and evaluate its effects on neurite and axon regeneration in vitro. Although AAV.miR-17 had no significant effect on neurite outgrowth and arborization, it significantly enhances neurite regeneration after scratch lesion and axon regeneration after axotomy of neurons cultured in microfluidic chambers. Target prediction and functional annotation analyses suggest that miR-17 regulates gene expression associated with autophagy and cell metabolism. Our findings suggest that miR-17 promotes regenerative response and thus could mitigate neurodegenerative effects.

MiR-155 enhances apoptosis of macrophage through suppressing PI3K-AKT activation in Pseudomonas aeruginosa keratitis

Keratitis induced by Pseudomonas aeruginosa (P. aeruginosa) is an acute and serious corneal inflammation. As a family of gene regulators, miRNAs play a crucial role in modulating host response after microbial invasion. However, their functions in P. aeruginosa keratitis remain largely unclear. In the present study, we demonstrated that miR-155 expression was significantly increased in macrophages and corneal tissue after P. aeruginosa infection. In vivo studies demonstrated that mice with miR-155 knockdown displayed more resistance to P. aeruginosa keratitis, with a lower bacterial burden. In addition, in vitro and in vivo studies indicated that miR-155 enhanced apoptosis of macrophages after P. aeruginosa infection, and resulted in a susceptible phenotype of P. aeruginosa keratitis. Moreover, miR-155 induced apoptosis through reducing activation of PI3K-Akt signaling pathway. Our data provided evidence of miR-155 mediated apoptosis of macrophage in P. aeruginosa keratitis, which may be an underlying target for the therapy of P. aeruginosa keratitis and other infectious diseases.

The Regulation of MicroRNA-21 by Interleukin-6 and Its Role in the Development of Fibrosis in Endometriotic Lesions.

Endometriosis is one of the most common causes of chronic pelvic pain and infertility that affects 10% of women of reproductive age. It is currently defined as the presence of endometrial epithelial and stromal cells at ectopic sites; however, advances in endometriosis research have some authors believing that endometriosis should be re-defined as "a fibrotic condition in which endometrial stroma and epithelium can be identified". microRNAs (miRNAs) are regulatory molecules that potentially play a role in endometriotic lesion development. There is evidence that suggests that miRNAs, including microRNA-21 (miR-21), participate in fibrotic processes in different organs, including the heart, kidney, liver and lungs. The objective of this study was to understand the role of miR-21 and the mechanisms that can contribute to the development of fibrosis by determining how IL-6 regulates miR-21 expression and how this miRNA regulates the transforming growth factor beta (TGF-β) signaling pathway to promote fibrosis. We investigated the expression of miR-21 in the baboon and mouse model of endometriosis and its correlation with fibrosis. We demonstrated that inflammation and fibrosis are present at a very early stage of endometriosis and that the inflammatory environment in the peritoneal cavity, which includes interleukin 6 (IL-6), can regulate the expression of miR-21 in vitro and in vivo.

Placental expressions of Anti-Mullerian hormone/Receptor, vascular endothelial growth factor and related microRNAs in patients with preeclampsia: a case control study

ABSTRACT Anti-Mullerian hormone (AMH) has been implicated in the pathogenesis of preeclampsia. The present study was primarily designed to determine the placental tissue AMH, Anti-Mullerian hormone Receptor II (AMHRII), vascular endothelial growth factor (VEGF) and microRNA (miRNA) 26a/126/155/210 expressions and serum miRNA 26a/126/155/210 levels in patients with preeclampsia to examine their potential role in the pathogenesis of preeclampsia. Placental tissue samples from patients with preeclampsia (n = 20) and control subjects (n = 20) were examined by immunohistochemical staining and quantitative polymerase chain reaction (qPCR) for AMH, AMHRII, VEGF mRNA expression levels and miRNA 26a/126/155/210 expressions. Serum levels of miRNA 26a/126/155/210 were measured by qPCR. Patients with preeclampsia had lower AMH/AMHRII immunostaining, particularly in syncytiotrophoblastic cells compared to control subjects (p < 0.05). The relative mRNA expressions of AMH/AMHRII were increased (1.535 ± 0.121 and 1.155 ± 0.049 fold, p < 0.0002 and p < 0.033, respectively) and the relative mRNA expression of VEGF was decreased (4.878 ± 0.331 fold, p < 0.0002) in patients with preeclampsia compared to control subjects. The miR-26a expression was increased and miR-126 expression was decreased in serum samples of patients with preeclampsia compared to control subjects (p < 0.0002). miR-155 and miR-210 expressions were increased in serum and placental tissue samples of patients with preeclampsia compared to control subjects (p < 0.0002). In conclusion, reduced placental tissue immunostaining of AMH/AMHRII along with increased AMH/AMHRII mRNA expressions may indicate posttranscriptional dysregulation. Robust increase in expressions of hypoxia/inflammation-related miRNAs particularly miR-155 and miR-210 might have a role in this mechanistic pathway. Increased serum levels of miR 26a, 155 and 210 are potential early diagnostic markers for preeclampsia.

The Overexpressed MicroRNAs miRs-182, 155, 493, 454, and U6 snRNA and Underexpressed let-7c, miR-328, and miR-451a as Potential Biomarkers in Invasive Breast Cancer and Their Clinicopathological Significance.

Breast cancer comprises the leading cause of cancer-related death in women. MicroRNAs (miRNAs) have emerged as important factors with concern to carcinogenesis and have potential for use as biomarkers. This study provides a comprehensive evaluation of the microRNA expression in invasive breast carcinoma of no special type tissues compared with benign tissues via large-scale screening and the candidate-specific validation of 15 miRNAs and U6 snRNA applying qPCR and the examination of clinicopathological data. Of the six downregulated miRNAs, let-7c was identified as the most promising miRNA biomarker and its lower expression was linked with Ki-67 positivity, luminal B versus luminal A samples, multifocality, lymph node metastasis, and inferior PFS. Of the 9 upregulated sncRNAs, the data on U6 snRNA, miR-493 and miR-454 highlighted their potential oncogenic functions. An elevated U6 snRNA expression was associated with the tumor grade, Ki-67 positivity, luminal B versus A samples, lymph node metastasis, and worsened PFS (and OS) outcomes. An elevated miR-454 expression was detected in higher grades, Ki-67 positive and luminal B versus A samples. Higher miR-493 levels were noted for the tumor stage (and grade) and worse patient outcomes (PFS, OS). The data also suggested that miR-451a and miR-328 may have tumor suppressor roles, and miR-182 and miR-200c pro-oncogenic functions, while the remaining sncRNAs did not evince any significant associations. We showed particular microRNAs and U6 snRNA as differentially expressed between tumors and benign tissues and associated with clinicopathological parameters, thus potentially corresponding with important roles in breast carcinogenesis. Their importance should be further investigated and evaluated in follow-up studies to reveal their potential in clinical practice.

Involvement of Expression of miR33-5p and ABCA1 in Human Peripheral Blood Mononuclear Cells in Coronary Artery Disease.

MicroRNAs (miRs) are small non-coding RNAs that regulate gene expression post-transcriptionally and are crucial in lipid metabolism. ATP-binding cassette transporter A1 (ABCA1) is essential for cholesterol efflux from cells to high-density lipoprotein (HDL). Dysregulation of miRs targeting ABCA1 can affect cholesterol homeostasis and contribute to coronary artery disease (CAD). This study aimed to investigate the expression of miRs targeting ABCA1 in human monocytes, their role in cholesterol efflux, and their relationship with CAD. We included 50 control and 50 CAD patients. RT-qPCR examined the expression of miR-33a-5p, miR-26a-5p, and miR-144-3p in monocytes. Logistic regression analysis explored the association between these miRs and CAD. HDL's cholesterol acceptance was analyzed using the J774A.1 cell line. Results showed that miR-26a-5p (p = 0.027) and ABCA1 (p = 0.003) expression levels were higher in CAD patients, while miR-33a-5p (p < 0.001) levels were lower. Downregulation of miR-33a-5p and upregulation of ABCA1 were linked to a lower CAD risk. Atorvastatin upregulated ABCA1 mRNA, and metformin downregulated miR-26a-5p in CAD patients. Decreased cholesterol efflux correlated with higher CAD risk and inversely with miRs in controls. Reduced miR-33a-5p expression and increased ABCA1 expression are associated with decreased CAD risk. miR deregulation in monocytes may influence atherosclerotic plaque formation by regulating cholesterol efflux. Atorvastatin and metformin could offer protective effects by modulating miR-33a-5p, miR-26a-5p, and ABCA1, suggesting potential therapeutic strategies for CAD prognosis and treatment.

Lnc NBAT1 Inhibits the Proliferation and Migration of Liver Cancer Cells Through the miR-21/PDCD4/AP-1 Signaling Axis.

Long non-coding RNAs (Lnc RNAs) are proven to participate in liver cancer (LC) regulation. The regulation of miR-21 by lnc NBAT1 has been studied in other cancers. However, the effect of this regulation on LC and its specific mechanism remains unclear. Lnc NBAT1 and miR-21 expressions in clinical tissues were measured by RT-qPCR. PDCD4, AP-1, p-c-Fos, p-c-Jun, and cyclin D1 expressions were analyzed by Western blot. Overexpression of lnc NBAT1 was studied to explore its influence on malignant behaviors of Bel7402 cells and the development of LC in the xenograft mouse model (XMM). The regulation mechanism of lnc NBAT1 in LC was explored by lnc NBAT1 overexpression, miR-21 mimic treatment, or PDCD4 silencing in Bel7402 cells. Lnc NBAT1 expression was downregulated while miR-21 expression was upregulated in LC tissues and cell lines. In comparison with LX-2 cells, the expressions of PDCD4 and AP-1 were downregulated in Bel7402 cells, while those of p-c-Fos, p-c-Jun, and cyclin D1 were upregulated. Further, lnc NBAT1 was found to localize primarily in the cytoplasm of Bel7402 cells. Overexpression of lnc NBAT1 enhanced cell apoptosis, blocked the cell cycle, suppressed malignant behaviors of Bel7402 cells, and inhibited tumor progression in the XMM. Mechanistically, lnc NBAT1 functioned as a competing endogenous RNA (ceRNA) by binding to the downstream target miR-21 to stabilize the expressions of PDCD4 and AP-1, thereby inhibiting malignant behaviors of Bel7402 cells. Lnc NBAT1 suppressed malignant behaviors of LC cells through the miR-21/PDCD4/AP-1 axis. Lnc NBAT1 might be a promising biomarker for LC treatment.

Abstract We129: Endothelium-Targeted MiR-122 Inhibition Improves Vascular Endothelial Function In a High-Fat Diet Fed mice

Background: MicroRNA-122-5p (miR-122), a liver-specific miR, levels are increased in the blood during obesity and diabetes and is taken-up by the extra-hepatic tissues including vascular endothelium. Despite miR-122’s role in maintaining hepatic homeostasis, its uptake (from circulation) by other tissues disrupts their function and increases the risk of cardiovascular disorders. Hence, inhibiting extra-hepatic miR-122 is a viable approach to mitigate vascular disorders associated with diabetes. Hypothesis: Endothelium-targeted miR-122 inhibitor selectively targets miR-122 in endothelial cells and improves vascular endothelial function in high-fat-diet (HFD) fed pre-diabetic mice. Methods: To selectively inhibit miR-122 in the endothelial cells, we synthesized gamma-peptide nucleic acid miR-122 inhibitor (γP-122 I) tagged with vascular cell adhesion molecule 1 (VCAM1) targeted peptide (e-γP-122 I). The purity was assessed using HPLC. Pre-diabetic condition was induced by feeding mice with a HFD (for 8 weeks) and e-γP-122-I was injected to the HFD-fed mice (2 weeks after dietary intervention; 5 mg/kg/day, i.p., 6 weeks). MiR-122 expression was measured by real-time PCR. The vascular endothelial function was assessed by determining endothelium-dependent and independent relaxation of phenylephrine-induced precontracted aortic rings. Results were expressed as mean ± s.e.m. Results: The e-γP-122-I was &gt;95% pure. The HFD-fed mice show higher levels of serum and aortic miR-122 expression and impaired vascular endothelial function. e-γP-122-I treatment selectively inhibited aortic miR-122 expression while it has no effect on other organs (heart, kidney etc.) and improved vascular endothelial function and inflammation. Conclusions: e-γP-122-I selectively inhibits miR-122 in the endothelium and improves endothelial function in pre-diabetic mice.

Abstract Tu147: Serial measurement of circulating cardiovascular enriched miR-1 and -34a reflects the changes in cardiac function in patients with ischemic heart disease – a five year follow-up study

Background: Patients with ischemic heart disease (IHD) require frequent monitoring, as the transition from stable disease to acute life-threatening events remains largely unpredictable. Currently available tests are either not sensitive enough to detect early changes or not easily incorporated into routine clinical practice. MicroRNAs (miRNAs), small non-coding RNAs involved in both physiological and pathological processes, are released into circulation and remain stable. Research Question: In this study, we aimed to determine if the serial measurement of cardiovascular-enriched circulating miRNAs could reflect changes in cardiac function in patients with IHD. Methods: Fifty-four new IHD patients joined a 5-year study, providing informed consent for regular echocardiography, blood tests and follow-ups at 12-month intervals. Plasma RNA was extracted and RT-PCR analysis used to assess expression of cardiovascular-enriched miR-1, miR-126, miR-132, and miR-34a. Results: Serial echocardiography analysis showed the development of diastolic dysfunction in the participants starting from 48 months (E/e’-10.7±4.3 vs 9.7±3.6 at baseline, P&lt;0.04). RT-PCR analysis revealed significant downregulation of miR-1 and miR-126 starting from 24 months of follow-up (P&lt;0.03 vs. baseline). Associations between each miRNA and each cardiac function measure were examined using linear mixed models without and with adjustment for changes in BMI and HbA1c during the same period. None of the lagged models found statistically significant associations (all p ≥ 0.126). From the concurrent models, two miRNA were associated with cardiac function: miR-1 and MV E Vel in the unadjusted (p = 0.045) and adjusted models (slope = -0.004, 95% CI -0.007 to -0.000, p = 0.026) models and miR-34a and FS(%) in the adjusted model only (slope = -0.151, 95% CI -0.301 to -0.001, p = 0.048). Conclusion: Results from this first-ever five-year follow-up study have identified a link between cardiovascular enriched miRNAs, miR-1 and -34a and cardiac function in patients with IHD, providing a knowledge platform for prognostic tests for IHD and laying the foundation for further studies in larger population size.

Translational modeling-based evidence for enhanced efficacy of standard-of-care drugs in combination with anti-microRNA-155 in non-small-cell lung cancer

BackgroundElevated microRNA-155 (miR-155) expression in non-small-cell lung cancer (NSCLC) promotes cisplatin resistance and negatively impacts treatment outcomes. However, miR-155 can also boost anti-tumor immunity by suppressing PD-L1 expression. Therapeutic targeting of miR-155 through its antagonist, anti-miR-155, has proven challenging due to its dual molecular effects.MethodsWe developed a multiscale mechanistic model, calibrated with in vivo data and then extrapolated to humans, to investigate the therapeutic effects of nanoparticle-delivered anti-miR-155 in NSCLC, alone or in combination with standard-of-care drugs.ResultsModel simulations and analyses of the clinical scenario revealed that monotherapy with anti-miR-155 at a dose of 2.5 mg/kg administered once every three weeks has substantial anti-cancer activity. It led to a median progression-free survival (PFS) of 6.7 months, which compared favorably to cisplatin and immune checkpoint inhibitors. Further, we explored the combinations of anti-miR-155 with standard-of-care drugs, and found strongly synergistic two- and three-drug combinations. A three-drug combination of anti-miR-155, cisplatin, and pembrolizumab resulted in a median PFS of 13.1 months, while a two-drug combination of anti-miR-155 and cisplatin resulted in a median PFS of 11.3 months, which emerged as a more practical option due to its simple design and cost-effectiveness. Our analyses also provided valuable insights into unfavorable dose ratios for drug combinations, highlighting the need for optimizing dose regimens to prevent antagonistic effects.ConclusionsThis work bridges the gap between preclinical development and clinical translation of anti-miR-155 and unravels the potential of anti-miR-155 combination therapies in NSCLC.

Expression analysis of microRNAs and cytokine mRNAs in pregnancies complicated by gestational hypertension

ObjectivesGestational hypertension (GH11GH − gestational hypertension) is one of the most common pregnancy-related complications, however, there is still insufficient knowledge about its development and molecular changes. The aim of our study was to examine the expression of miR-17, miR-29a and miR-181a, as well as TNF-α, IL-1β, IL-6 and IL-17 in women with GH and to investigate possible correlations between these parameters. Study designThe study included 64 pregnant women, placed either in the control or the GH group. Quantitative real-time PCR (qPCR22qPCR − quantitative real-time PCR.) was used to determine expression levels of microRNAs and cytokines’ mRNAs. Main outcome measuresExpression levels of miRNAs (miR-17, miR-29a and miR-181a) and proinflammatory cytokines mRNAs (TNF-α, IL-1β, IL-6 and IL-17) in women with gestational hypertension were compared to the control group (healthy pregnant women). ResultsNo significant changes in microRNAs expression level were found between compared groups. TNF-α was significantly upregulated in the GH group compared to controls. Expression levels of other investigated cytokines did not differ between examined groups. ROC curve analysis indicated that TNF-α does not show sufficient ability to discriminate between CG and GH patients. TNF-α was significantly positively correlated with IL-1β and IL-17 and negatively correlated with miR-181a. ConclusionsOur results point to the involvement of proinflamatory cytokines in gestational hypertension. Although increased expression of TNF-α was found in the GH group, this cytokine did not show sufficient ability to discriminate between GH and healthy pregnancies.

Abstract Tu001: MiR-21 mitigated pulmonary hypertension induced right ventricular dysfunction through pulmonary circulating exosomes

Background: Patients with pulmonary arterial hypertension (PAH) often experience adverse outcomes primarily due to right ventricular (RV) dysfunction. However, the intricate relationship between pulmonary circulation and RV remodeling remains largely unexplored. Exosomal microRNAs (miRNAs) function as paracrine signaling mediators in diverse diseases. Aims: To investigate the ability of exosomal miRNAs derived from pulmonary endothelial cells to transmit signals affecting cardiomyocytes. Methods and Results: Utilizing next-generation sequencing, we identified several target miRNAs by analyzing exosome samples obtained through right-heart catheterization. Notably, exosomal miR-21 exhibited the highest expression in the pulmonary circulation (Figure 1) . Under hypoxic conditions, the expression of miR-21 increased in human pulmonary endothelial cells (HPECs) and in exosomes derived from their conditioned medium. Treatment with these exosomes enhanced miR-21 expression and concurrently mitigated apoptosis in hypoxia-exposed cardiomyocytes. Likewise, miR-21 demonstrated a protective role against hypoxia-induced injuries and apoptosis, involving the SPRY-2/p-ERK and PTEN/Akt pathways. In a murine model of sugen/hypoxia-induced PAH, mice lacking miR-21 (miR-21 -/- ) exhibited more severe RV dysfunction, altered hemodynamics, and increased fibrosis compared to wild-type (WT) mice. Employing a parabiosis model, pairs consisting of WT and miR-21 -/- mice were shielded from RV dysfunction, whereas pairs of miR-21 -/- mice displayed exacerbated RV function (Figure 2) . Conclusion: Hypoxia stimulates the production of exosomal miR-21 in both HPECs and their microenvironment, subsequently mitigating apoptosis in cardiomyocytes (Figure 3) . Our findings propose endothelial cell-derived exosomal miR-21 as a promising therapeutic target for PAH.

MiR-21 attenuated inflammation targeting MyD88 in human chondrocytes stimulated with Hyaluronan oligosaccharides

Inflammation is the body's response to injuries, which depends on numerous regulatory factors. Among them, miRNAs have gained much attention for their role in regulating inflammatory gene expression at multiple levels. In particular, miR-21 is up-regulated during the inflammatory response and reported to be involved in the resolution of inflammation by down-regulating pro-inflammatory mediators, including MyD88. Herein, we evaluated the regulatory effects of miR-21 on the TLR-4/MyD88 pathway in an in vitro model of 6-mer HA oligosaccharides-induced inflammation in human chondrocytes.The exposition of chondrocytes to 6-mer HA induced the activation of the TLR4/MyD88 pathway, which culminates in NF-kB activation. Changes in miR-21, TLR-4, MyD88, NLRP3 inflammasome, IL-29, Caspase1, MMP-9, iNOS, and COX-2 mRNA expression of 6-mer HA-stimulated chondrocytes were examined by qRT-PCR. Protein amounts of TLR-4, MyD88, NLRP3 inflammasome, p-ERK1/2, p-AKT, IL-29, caspase1, MMP-9, p-NK-kB p65 subunit, and IKB-a have been evaluated by ELISA kits. NO and PGE2 levels have been assayed by colorimetric and ELISA kits, respectively.HA oligosaccharides induced a significant increase in the expression of the above parameters, including NF-kB activity. The use of a miR-21 mimic attenuated MyD88 expression levels and the downstream effectors. On the contrary, treatment with a miR-21 inhibitor induced opposite effects. Interestingly, the use of a MyD88 siRNA confirmed MyD88 as the target of miR-21 action.Our results suggest that miR-21 expression could increase in an attempt to reduce the inflammatory response, targeting MyD88.

AB062. Investigating miR-21 as a non-invasive prognostic biomarker in glioma patients.

Glioma prognosis remains a challenge due to its high recurrence and resistance to treatment. Diagnosis and follow-up in resource-constrained regions often lead to significant patient attrition. Serum microRNAs (miRNAs) are seen to be aberrantly expressed in malignancies can be found in tumor tissues and peripheral samples. This offers a pathway for non-invasive liquid biopsies. miR-21 is an established biomarker for glioma prognosis, which needs to be validated in our population. We collected 89 intraoperative tumor tissue samples, and 42 pre- and post-operative serum samples from glioma patients, ten control tissues, eight healthy serum samples and analysed for miR-21 expression through quantitative polymerase chain reaction (qPCR) analysis. Correlational analysis with molecular markers isocitrate dehydrogenase (IDH), Ki-67, ATRX, p53, and survival curves through the Kaplan-Meier method were calculated in high and low miR-21 expression groups. The hazard ratio was quantitatively determined using Cox regression analysis, considering both univariate associations and multivariate correlations with clinical parameters. miR-21 expression in tissue was significantly upregulated with increase of glioma grades (P<0.001) and in patients above 50 years (P=0.003) age group. Whereas no gender bias was seen in its expression pattern. Its expression did not show any correlation with tumor volume (r=0.22, P=0.08). A similar expression pattern of miR-21 was observed in serum samples of glioma. IDH-wildtype (P=2.06e-03) and high Ki-67 (P=2.50e-03) patient group showed significant upregulation of miR-21 expression compared to IDH-mutant and low Ki-67 group. Patients with low miR-21 expression had significantly longer overall survival (OS) than patients with high miR-21 expression (P =0.006). Similarly, quantitative hazard analysis indicates that patients in the high expression group have 2.77 times higher risk of mortality [95% confidence interval (CI): 0.19-0.92], in comparison to patients in the low expression group (P=0.008). Our findings validate the utility of miR-21 as a prognostic serum biomarker to help diagnose and assess treatment response in advancing glioma grades, within our population.

Evaluation of the Plasma Expression Levels of miR-21 and miR-145 as Potential Non-Invasive Biomarkers for Early Detection of Colorectal Cancer.

Colorectal cancer (CRC) is one of the most commonly diagnosed cancers in the world. Early detection would be greatly enhanced if accurate and cost-effective diagnostic biomarkers for CRC were accessible. The development of blood tests would evidently lower the screening cost of CRC detection. The aim of the present study was to examine the prospective of plasma miRNAs as non-invasive biomarkers for CRC screening. The expressions of miR-21 and miR-145 in the plasma of colorectal adenocarcinomas and normal healthy controls were quantified by using TaqMan miRNA assays. MiRNA expression levels were also correlated with commonly used clinicopathological features of CRC. Out of 30 CRC patients, 19 were male and 11 were female. The Mean age of patients was 51.3 ±14.6 years. A statistically significant increase in expression of miR-21 was observed in CRC patients' as compared to healthy controls (p<0.001). A significant association between miR-21 expression and age group (p=0.002) was noticed. Also, a statistically significant difference (p=0.015) between miR-21 expression and tumor location in the proximal and distal sites of the colon was observed in CRC patients. Further, a statistically significant downregulation of miR-145 expression was observed in the plasma of CRC patients as compared to healthy controls (p<0.05). This is the first study to report a significant association between miR-21 expression, age group, and tumor location in CRC patients. The present study thus emphasises that the appraisal of miR-21 and miR-145 plasma levels may serve as a promising non-invasive screening tool for the early detection of colorectal cancer.

Expression of Circulating miR-21 and -29 and their Association with Myocardial Fibrosis in Hypertrophic Cardiomyopathy.

Hypertrophic Cardiomyopathy (HCM) is characterized by myocardial hypertrophy, fibrosis, and sarcomeric disarray. To evaluate the expression levels of circulating miR-21 and -29 in patients with HCM and their association with clinical characteristics and myocardial fibrosis. In this case-control study, 27 subjects with HCM, 13 subjects with hypertensive cardiomyopathy, and 10 control subjects were enrolled. Evaluation of patients' functional capacity was made by the six-minute walk test. Echocardiographic measurements of left ventricle systolic and diastolic function were conducted. Cardiac magnetic resonance late gadolinium enhancement (LGE) -through a semiquantitative evaluation- was used in the assessment of myocardial fibrosis extent in HCM patients. The expression of miR-21 and -29 in peripheral blood samples of all patients was measured via the method of quantitative reverse transcription polymerase chain reaction. Circulating levels of miR-21 were higher in both hypertensive and HCM (p<0.001) compared to controls, while expression of miR-29 did not differ between the three studied groups. In patients with HCM and LGE-detected myocardial fibrosis in more than 4 out of 17 myocardial segments, delta CT miR-21 values were lower than in patients with myocardial LGE in 3 or fewer myocardial segments (2.71 ± 1.06 deltaCT vs. 3.50 ± 0.55 deltaCT, p<0.04), indicating the higher expression of circulating miR-21 in patients with more extensive myocardial fibrosis. MiR-21 was overexpressed in patients with HCM and hypertensive cardiomyopathy. Importantly, in patients with HCM, more extensive myocardial fibrosis was associated with higher levels of miR-21.

M1 Macrophage-Derived Exosomal MiR-155 Enhances Autophagy in Sepsis-Triggered Acute Kidney Injury

Sepsis-induced Acute kidney injury (SA-AKI), a common complication in sepsis, significantly impacts patients’ health and quality of life. M1 macrophages have been demonstrated to release inflammatory mediators that exacerbate kidney injury. MiR-155 has been implicated in promoting inflammation and damage during sepsis while reducing miR-155 levels alleviates SA-AKI. However, the relationship between miR-155 and M1 macrophage-derived exosomes in regulating autophagy during SA-AKI remains unclear. In this study, we aim to investigate the relationship between M1 macrophage-derived exosomes and miR-155 in regulating autophagy during SA-AKI. A mouse model of SA-AKI was established by performing cecal ligation and puncture (CLP) surgery. Additionally, the HK-2 cell line was utilized to establish a sepsis cell model by inducing lipopolysaccharide (LPS). We demonstrated that the mice model of SA-AKI exhibited renal injury along with enhanced autophagy, inflammation response, and macrophage polarization after CLP surgery. M1 macrophages attenuated cell viability and enhanced autophagy in LPS-treated HK-2 cells. Additionally, M1 macrophage-derived exosomes were observed to enhance autophagy in LPS-treated HK-2 cells. Furthermore, we confirmed an increased expression of miR-155 in M1 macrophage-derived exosomes. Furthermore, exosome-mediated miR-155 enhanced autophagy in LPS-treated HK-2 cells. In conclusion, this study provides the first evidence that exosomal miR-155 derived from M1 macrophages enhances autophagy in SA-AKI. These findings suggest that targeting exosomal miR-155 could be a promising therapeutic strategy for SA-AKI.

Targeting miR-29 mitigates skeletal senescence and bolsters therapeutic potential of mesenchymal stromal cells

Mesenchymal stromal cell (MSC) senescence is a key factor in skeletal aging, affecting the potential of MSC applications. Identifying targets to prevent MSC and skeletal senescence is crucial. Here, we report increased miR-29 expression in bone tissues of aged mice, osteoporotic patients, and senescent MSCs. Genetic overexpression of miR-29 in Prx1-positive MSCs significantly accelerates skeletal senescence, reducing cortical bone thickness and trabecular bone mass, while increasing femur cross-sectional area, bone marrow adiposity, p53, and senescence-associated secretory phenotype (SASP) levels. Mechanistically, miR-29 promotes senescence by upregulating p53 via targeting Kindlin-2 mRNA. miR-29 knockdown in BMSCs impedes skeletal senescence, enhances bone mass, and accelerates calvarial defect regeneration, also reducing lipopolysaccharide (LPS)-induced organ injuries and mortality. Thus, our findings underscore miR-29 as a promising therapeutic target for senescence-related skeletal diseases and acute inflammation-induced organ damage.

MiR-29a expression negatively correlates with Bcl-2 levels in colorectal cancer and is correlated with better prognosis

MicroRNAs (miRNAs) are a class of small non-coding RNAs that act as important regulators of gene expression, involved in various biological pathways. Aberrant miRNAs expression is associated with the onset and progression of colorectal cancer (CRC). The aim of this study was to investigate the correlation between five miRNAs (miR-29a, miR-101, miR-125b, miR-146a, and miR-155), found to be deregulated in tissue samples of CRC patients, and clinicopathological characteristics and histological markers. Analysis of histological markers was performed by immunohistochemical staining of tumour tissues with Ki-67, p53, CD34, and Bcl-2. Our findings revealed a significant negative correlation between miR-29a expression and Bcl-2 levels. Furthermore, high miR-29a expression was associated with a lower incidence of distant metastasis in CRC patients. We observed negative correlations between miR-101 expression and the number of lymph nodes with metastasis, as well as the size of the largest metastasis; miR-125b expression and lymphovascular invasion; and miR-155 expression and mucus presence. Our survival analysis demonstrated that high miR-29a expression correlated with better progression-free survival of CRC patients, underscoring its potential as a prognostic marker. Our study unveiled intricate relationships between specific miRNA expressions and clinicopathological features in CRC, highlighting the potential utility of miR-29a as a valuable prognostic biomarker.

The Role of the MiR-181 Family in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the fourth-leading cause of cancer-related death worldwide. Due to the high mortality rate in HCC patients, discovering and developing novel systemic treatment options for HCC is a vital unmet medical need. Among the numerous molecular alterations in HCCs, microRNAs (miRNAs) have been increasingly recognised to play critical roles in hepatocarcinogenesis. We and others have recently revealed that members of the microRNA-181 (miR-181) family were up-regulated in some, though not all, human cirrhotic and HCC tissues-this up-regulation induced epithelial-mesenchymal transition (EMT) in hepatocytes and tumour cells, promoting HCC progression. MiR-181s play crucial roles in governing the fate and function of various cells, such as endothelial cells, immune cells, and tumour cells. Previous reviews have extensively covered these aspects in detail. This review aims to give some insights into miR-181s, their targets and roles in modulating signal transduction pathways, factors regulating miR-181 expression and function, and their roles in HCC.