Expression Of miR-125b Research Articles

MiR-23b/TAB3/NF-κB/p53 axis is involved in hippocampus injury induced by cerebral ischemia-reperfusion in rats: The protective effect of chlorogenic acid.

Apoptosis is the main pathological aspect of neuronal injury after cerebral ischemia-reperfusion (I/R) injury. However the detailed molecular mediators are still under debate. The aim of this study is to explore the effect of cerebral I/R on miR-23a/TGF-β-activated kinase 1 binding protein 3 (TAB3)/nuclear factor kappa B (NF-κB)/p53 axis in rat hippocampus alone and in combination with chlorogenic acid (CGA). Common carotid artery occlusion (CCAO) was performed by nylon monofilament for 20 min to establish a model of ischemic brain injury. CGA (30 mg/kg) was administered intraperitoneally (ip), 10min prior to ischemia and 10min before reperfusion. Examination of hippocampus neurons by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining showed that the number of apoptotic neurons was elevated at 24 h after reperfusion. At the molecular levels, I/R injury resulted in an increased protein expression of p53 with a concomitant upregulation of cleaved-caspase3/phosphorelated-caspase3 ratio and cytochrome c level. Further miR-23b gene expression was significantly downregulated after 24 h of reperfusion. Also, we observed increased TAB3 and NF-κB protein expressions after 24 h following CCAO. Treatment with CGA significantly reduced the apoptotic damage and also reversed miR-23b gene expression, TAB3 and NF-κB protein expressions in hippocampus neurons in I/R rats. In conclusion our data suggest that miR-23b/TAB3/NF-κB/p53 axis could play a regulatory role in hippocampus cell death, which provide a new target for novel therapeutic interventions during transit ischemic stroke. It also demonstrated that CGA could reverse these molecular alterations indicating an effective component against hippocampus apoptotic insult following acute I/R injury.

MiR-155: A Potential Biomarker for Predicting Mortality in COVID-19 Patients.

COVID-19, a pandemic of severe acute respiratory syndrome caused by Coronavirus 2 (SARS-CoV-2), continues to pose diagnostic and therapeutic challenges due to its unpredictable clinical course. Prognostic biomarkers may improve care by enabling quick identification of patients who can be safely discharged home versus those who may need careful respiratory monitoring and support. MicroRNAs (miRNAs) have risen to prominence as biomarkers for many disease states and as tools to assist in medical decisions. In the present study, we aimed to examine circulating miRNAs in hospitalized COVID-19 patients and to explore their potential as biomarkers for disease severity. We studied, by quantitative PCR, the expressions of miR-21, miR-146a, miR-146b, miR-155, and miR-499 in peripheral blood. We found that mild COVID-19 patients had 2.5-fold less circulating miR-155 than healthy people, and patients with a severe COVID-19 disease had 5-fold less circulating miR-155 than healthy people. In addition, we found that miR-155 is a good predictor of COVID-19 mortality. We suggest that examining miR-155 levels in patients’ blood, upon admission to hospital, will ameliorate the care given to COVID-19 patients.

Long non-coding RNA BBOX1 antisense RNA 1 increases the apoptosis of granulosa cells in premature ovarian failure by sponging miR-146b

ABSTRACT Long non-coding RNA (lncRNA) BBOX1 antisense RNA 1 (BBOX1-AS1) was reported to participate in ovarian cancer, while its role in other ovarian disorders is unclear. We speculated that BBOX1-AS1 could interact with microRNA(miR)-146b, which is involved in premature ovarian failure (POF). This study was therefore carried out to explore its role in POF. In this study, 60 patients with POF and 60 controls were enrolled. The expression of BBOX1-AS1 and miR-146b were analyzed by RT-qPCRs. The direct interaction between miR-146b and the wild type BBOX1-AS1 (BBOX1-AS1-WT) or mutant BBOX1-AS1 (BBOX1-AS1-mut) was explored with RNA-RNA pulldown assay. Subcellular location of BBOX1-AS1 in COV434 granulosa cells was detected by subcellular fractionation. The role of BBOX1-AS1 and miR-146b in the apoptosis of COV434 cells was evaluated by cell apoptosis assay. Overexpression assay was applied to explore the relationship between BBOX1-AS1 and miR-146b. We found that the expression levels of BBOX1-AS1 were increased, while the expression levels of miR-146b were decreased in POF patients. BBOX1-AS1-WT, but not BBOX1-AS1-mut, directly interacted with miR-146b. BBOX1-AS1 was detected in both nucleus and cytoplasm, while they did not affect the expression of each other. BBOX1-AS1 suppressed the role of miR-146b in cell apoptosis. Therefore, BBOX1-AS1 may increase the apoptosis of granulosa cells in POF by sponging miR-146b.

MicroRNA-199b Deregulation Shows Oncogenic Properties and Promising Clinical Value as Circulating Marker in Locally Advanced Rectal Cancer Patients.

The identification of robust prognostic markers still represents a need in locally advanced rectal cancer (LARC). MicroRNAs (miRs) have progressively emerged as promising circulating markers, overcoming some limitations that traditional biopsy comprises. Tissue miR-199b deregulation has been reported to predict outcome and response to neoadjuvant chemoradiotherapy (nCRT) in LARC, and was also found to be associated with disease progression in colorectal cancer. However, its biological and clinical relevance remains to be fully clarified. Thus, we observed here that miR-199b regulates cell migration, aggressiveness, and cell growth, and inhibits colonosphere formation and induces caspase-dependent apoptosis. Moreover, miR-199b expression was quantified by real-time PCR in plasma samples from LARC patients and its downregulation was observed in 22.7% of cases. This alteration was found to be associated with higher tumor size (p = 0.002) and pathological stage (p = 0.020) after nCRT. Notably, we observed substantially lower global miR-199b expression associated with patient downstaging (p = 0.009), as well as in non-responders compared to those cases who responded to nCRT in both pre- (p = 0.003) and post-treatment samples (p = 0.038). In concordance, we found that miR-199b served as a predictor marker of response to neoadjuvant therapy in our cohort (p = 0.011). Altogether, our findings here demonstrate the functional relevance of miR-199b in this disease and its potential value as a novel circulating marker in LARC.

RETRACTED ARTICLE: Evaluating the role of propolis and bee venom on the oxidative stress induced by gamma rays in rats

Honeybee products consist of many substances, which have long been known for their medicinal and health-promoting properties. This study set out to appraise the protective potential of Egyptian propolis (EP) and bee venom (BV) separately or combined against total body irradiation (TBI) induced oxidative injury in rats. Besides, we assessed the bioactive components in EP and BV using HPLC and UPLC/ ESI–MS analysis in the positive ion mode. The animals were subjected to a source of gamma ionizing radiation at a dose of 6 Gy. Propolis and BV were administered independently and in combination before 14 days of γ-irradiation. Liver and kidney functions were estimated besides, DNA damage index (8- OHdG) by ELISA. Antioxidants, including glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) were detected. Gene expression technique investigated for BAX, BCL2, and in plasma also miR125b expression in serum of rats. Besides, the histopathological for the brain, liver, kidney, and heart were investigated. In addition, lipid peroxidation was investigated in plasma and in the previous organs. The present results provide opportunities to advance the use of bee products as promising medicinal sources.

The role of exosomal miR-181b in the crosstalk between NSCLC cells and tumor-associated macrophages.

It has been reported that tumor-associated macrophages (TAMs) participate in modulating the progression of cancer in the tumor microenvironment. However, the crosstalk between TAMs and non-small cell lung cancer (NSCLC) is still unclear. We investigated whether NSCLC-derived exosomes could affect TAMs, which feedback modulated progression of NSCLC. MiR-181b expression was measured by RT-PCR. Human THP-1 monocyte was differentiated into macrophages with phorbol myristate acetate, which were further identified by transmission electron microscopy and western blot. Macrophage M1 and M2 polarizations were detected by flow cytometry, RT-PCR and western blot. Proliferation, migration, and invasion of NSCLC cells treated with conditioned mediums were detected by EdU and Transwell assays. We demonstrated that miR-181b was up-regulated in exosomes derived from NSCLC patients' serum and NSCLC cells. MiR-181b could be transferred to macrophages via exosomes in the co-culture system of macrophages and NSCLC cells, which promoted macrophage M2 polarization. Further examinations revealed that exosomes derived from NSCLC cells could enhanced macrophage M2 polarizations by regulating miR-181b/JAK2/STAT3 axis, and silencing miR-181b in NSCLC cells and JAK2 inhibitor used in macrophages could reverse the effects. Importantly, the conditioned medium of macrophages treated with NSCLC cell-derived exosomes could promote NSCLC cell proliferation, migration, and invasion. Silencing miR-181b in NSCLC cells and JAK2 inhibitor used in macrophages could block the effects. All of these results indicated that exosomal miR-181b participated in the crosstalk between NSCLC cells and TAMs, providing potential therapeutic targets for NSCLC.

Association between extract of Euphorbia szovitsii and expression level of microRNAs in MDA-MB-231 cell line.

The miRNAs have been shown to be involved in breast cancer. The aim of the present research was to evaluate the impacts of extract from Euphorbia szovitsii Fisch & C.A. Mey on the expression level of microRNAs in triple-negative breast cancer (MDA-MB-231) cell line. The alterations in the expression level of miRNAs in MDA-MB-231 cell line exposed to the extract of E. szovitsii were determined exploiting qRT-PCR technique. The expression of MDA-MB-231 cell microRNAs including miR-15, miR-16, miR-21, miR-29, miR-34a, miR-146b, miR-151, miR-155, miR-181b, miR-221, miR-222, and Let-7 was evaluated at 24 and 48h after treatment with the E. szovitsii extract. The treatment of MDA-MB-231 cells with E. szovitsii caused a significant elevation in the expression of miR-155, miR-146b (P < 0.05), miR-16, miR-21, miR-151(P < 0.01), and miR-34a (P<0.001) after 24h, and alsomiR-155, Let-7 (P<0.05), miR-15, miR-29, miR-151 (P<0. 01), miR-146b and miR-34a (P<0.001) after 48h. The qRT-PCR findings at 24 and 48h after treatment revealed that the MDA-MB-231 cell line in the presence of E. szovitsii extract showed an alteration in the expression profile of miRNAs implicated in the induction of cell proliferation, apoptosis and migration. These results may be helpful in determining the anticancer activity of E. szovitsii in MDA-MB-231 cell line.

BAG2-activated cell autophagy and mir-27b dynamic regulation mechanism during Mycobacterium tuberculosis infection.

Tuberculosis is a highly contagious infectious disease. Mycobacterium tuberculosis infection is the main cause of tuberculosis. During the infection of M. tuberculosis, the expression of the resistance gene BAG2 will change, and miR-27b will play a certain role in dynamic regulation. The purpose of this article is to explore in-depth the effect of BAG2 on cell autophagy during M. tuberculosis infection and the dynamic regulatory mechanism of miR-27b on BAG2 activated cell autophagy. Fifty rats were used as experimental subjects, and M. tuberculosis strains H37Ra and H37Rv were implanted into the rats. Fluorescence quantitative PCR was used to detect the dynamic changes of BAG2 and miR-27b expression levels in rats and the regulatory effect of miR-27b on BAG2, and the effect of changes in BAG2 expression levels on cell autophagy was studied by immunoblotting. The results showed that after M. tuberculosis-infected macrophages, the expression level of BAG2 decreased from (284.24±6.31) to (156.48.24±4.49), and the expression level of miR-27b was increased from (43.72±3.35) to (78.35± 4.17), the apoptosis rate increased by 17.8%, and the autophagy rate increased by 20.6%. Therefore, it can be seen that the up-regulation of miR-27b expression level during M. tuberculosis infection will inhibit BAG2 expression, thereby promoting cell autophagy and apoptosis to reduce the survival rate of M. tuberculosis.

Expression of let-7a, miR-106b and miR-29b is changed in human gastric cancer.

MicroRNA (miRNA) are small, noncoding RNA sequences that post-transcriptionally regulate the proliferation, activity and apoptosis of human gastric cancer cells by controlling various signaling cascades. Processes that involve miRNA molecules can create a specific network of interactions in a cell, and disruption of its functioning may contribute to the transformation of normal cells into cancerous cells. Aims of our survey were: 1) study the relationship between the expression of selected miRNA types (let-7a, miR-106b, miR-29b, miR-21, miR-155, miR-222) in the gastric mucosa and pathomorphological changes determined by classical histopathological methods, 2) perform in silico analysis to select target genes for selected miRNAs and to perform functional analysis of these genes. Eighty-three subjects (45 women, 38 men; mean age 39±14 years, range: 21-80 years, were examined). Among them were 18 (21.5%) patients with chronic active gastritis, 42 (50.6%) people with chronic inactive gastritis, 9 (10.8%) patients with gastric cancer and 14 (16.9%) patients without histopathological changes. The study demonstrated that mainly the expression of 3 (miR-29b, let-7a miR-106b) out of 6 selected miRNAs are significantly different depending on the site of biopsy (body of the stomach or antrum) and the group of patients. Expression of miR-106b in the antrum and body was the highest in the group of cancer patients and the lowest in patients with chronic active gastritis. The expression of let-7a differed depending on group of patients and location. The highest expression was in the body in the group with inactive gastritis and the lowest in gastric cancer. Patients with cancer had the lowest expression of miR-29b in stomach body and it was the highest in the patients with inactive gastritis in this location. Expression of miR-21 and miR-155 determinations were not statistically significant in comparison to groups or locations, and of miR-222 was not different between the groups, but only in the control group was higher in the antrum than in the body. We conclude that identification of miRNAs may represent a promising modern complementary method in the diagnosis of gastric diseases, especially cancer.

Role of miR-15b/16–2 cluster network in endometrial cancer: An in silico pathway and prognostic analysis

Endometrial cancer (EC) is the second most common cancer in women. A large number of human cancers exhibit dysregulation of microRNA expression including EC. MiR-15b/16–2 is one of the best-known miRNA clusters that is expressed in many types of cancer tissues. Herein, we analyzed the expression of individual miR-15b/16–2 cluster members, its paralogues, and their target network analysis, as well as their prognostic significance in EC. UALCAN and GEPIA2 were used to analyze the expression of the individual members of the cluster. The gene target was predicted through miRTarBase, and the genes were then compared through the TCGA-UCEC dataset. The differential gene expression and network analysis identified 175 DEGs associated with critical cancer-related pathways. The prognostic significance and metastatic prediction were carried out using GEPIA2 and HCMDB tools. In UCEC patient samples, miR- 15b/16–2 cluster expression is negatively correlated with the overall survival of the patients. The uterus-specific miRNA-lncRNA, miRNA-circRNA, and miRNA-sncRNA networks of miR- 15b/16–2 cluster contain 1164 edges and nodes consisting of 5 sncRNA, 124 circRNA, and 1552 genes. The DEGs analysis led to the identification of SIPA1L2, PDCD1, CCNJ, ENTPD7, PLEKHA5, NPAS3, DPH5, BTF3, NPAS3, SENP2, and CCND3 as a significant predictor of overall survival in UCEC patients. The analysis of metastasis found 24 genes significantly associated with brain and lymph node metastasis. The analysis of drug-gene interactions revealed 267 FDA-approved drugs for treating cancers. Our data provided novel insight on the miR-15b/16–2 cluster role in EC and prioritized the findings for experimental verification. Besides, more comprehensive clinical and mechanistic studies are needed to confirm our findings in endometrial cancer.

Ranolazine Inhibits Pyroptosis via Regulation of miR-135b in the Treatment of Diabetic Cardiac Fibrosis.

Diabetic cardiomyopathy (DCM) is a major cardiovascular complication of diabetes mellitus (DM), and cardiac fibrosis is a characteristic pathological manifestation of DCM. DCM can be exacerbated by pyroptosis, and pyroptosis is a potential target of microRNAs (miRNAs). miR-135b is involved in delaying the progression of numerous cardiovascular diseases, Nonetheless, the role of miR-135b in diabetic cardiac fibrosis is unclear. Ranolazine is a piperazine derivative and is effective for the treatment of cardiovascular disease. The purpose of the study was to elucidate the mechanism of action of ranolazine against diabetic cardiac fibrosis and to investigate the role of miR-135b in this process. Functional and structural changes in the rat heart were examined by echocardiography, hematoxylin-eosin (H&E) and Masson staining. Immunohistochemistry was used to assess the expression of caspase-1, interleukin-1β (IL-1β), gasdermin D (GSDMD), transforming growth factor-β1 (TGF-β1), collagen I and collagen III in the rat left ventricle. Western blot and immunofluorescence were used to detect the protein expression of caspase-1, IL-1β, GSDMD, TGF-β1, collagen I and collagen III proteins, and the mRNA levels were determined using fluorescent quantitative PCR. Ranolazine reduced pyroptosis and inhibited collagen deposition, improving cardiac function in rats. Ranolazine increased miR-135b expression in high glucose-treated cardiac fibroblasts, and miR-135b directly bound to caspase-1. Interference with miR-135b reduced the effects of ranolazine on pyroptosis and collagen deposition. Ranolazine treatment of diabetic cardiac fibrosis inhibited pyroptosis and collagen deposition by upregulating miR-135b. Our study provides a solid theoretical basis for understanding the pathogenesis of diabetic cardiac fibrosis and the clinical use of ranolazine in the treatment of DCM.

Dynamic MicroRNA Expression Profiles During Embryonic Development Provide Novel Insights Into Cardiac Sinus Venosus/Inflow Tract Differentiation.

MicroRNAs have been explored in different organisms and are involved as molecular switches modulating cellular specification and differentiation during the embryonic development, including the cardiovascular system. In this study, we analyze the expression profiles of different microRNAs during early cardiac development. By using whole mount in situ hybridization in developing chick embryos, with microRNA-specific LNA probes, we carried out a detailed study of miR-23b, miR-130a, miR-106a, and miR-100 expression during early stages of embryogenesis (HH3 to HH17). We also correlated those findings with putative microRNA target genes by means of mirWalk and TargetScan analyses. Our results demonstrate a dynamic expression pattern in cardiac precursor cells from the primitive streak to the cardiac looping stages for miR-23b, miR-130a, and miR-106a. Additionally, miR-100 is later detectable during cardiac looping stages (HH15-17). Interestingly, the sinus venosus/inflow tract was shown to be the most representative cardiac area for the convergent expression of the four microRNAs. Through in silico analysis we revealed that distinct Hox family members are predicted to be targeted by the above microRNAs. We also identified expression of several Hox genes in the sinus venosus at stages HH11 and HH15. In addition, by means of gain-of-function experiments both in cardiomyoblasts and sinus venosus explants, we demonstrated the modulation of the different Hox clusters, Hoxa, Hoxb, Hoxc, and Hoxd genes, by these microRNAs. Furthermore, we correlated the negative modulation of several Hox genes, such as Hoxa3, Hoxa4, Hoxa5, Hoxc6, or Hoxd4. Finally, we demonstrated through a dual luciferase assay that Hoxa1 is targeted by miR-130a and Hoxa4 is targeted by both miR-23b and miR-106a, supporting a possible role of these microRNAs in Hox gene modulation during differentiation and compartmentalization of the posterior structures of the developing venous pole of the heart.

MicroRNA expression is deregulated by aberrant methylation in B-cell acute lymphoblastic leukemia mouse model.

The expression of microRNAs (miRNAs) in the serum of B-cell acute lymphoblastic leukemia (B-ALL) patients is abnormal. Nevertheless, the underlying mechanism remains unclear. Recent studies indicate that the methylation state of circulating cell-free DNA (cfDNA) is different between cancer patients and healthy individuals. Therefore, we speculate that abnormal expression of miRNA may be associated with cfDNA methylation. A green fluorescent protein (GFP) labeled B-ALL transplantation animal model was established to explore the relationship between the miRNA expression and cfDNA methylation of the related gene. Quantitative real-time PCR (qRT-PCR) was used to detect the expression levels of miRNAs. Further, cfDNA methylation levels of the related genes were evaluated through bisulfite sequencing polymerase chain reaction (BSP). The expression levels of miR-196b, miR-203, miR-34a-5p, miR-335-3p, miR-34b-5p, miR-615, miR-375-3p and miR-193b-5p in the serum of the model mice were significantly lower than those of the control group (P < 0.05). The methylation level of miR-196b promoter in cfDNA of the model group was significantly lower than that of the control group (P < 0.05), whereas no significant difference was noted in miR-203 promoter. The methylation levels of miR-196b and miR-203 coding region in cfDNA of the model group were significantly higher than those of the control group (P < 0.05). These results showed that CpG island hypermethylation in the miRNA coding region of cfDNA is related to the low expression of miR-196b and miR-203.

Transcription Factor Specificity Protein 1 Regulates Inflammation and Fibrin Deposition in Nasal Polyps Via the Regulation of microRNA-125b and the Wnt/β-catenin Signaling Pathway.

Nasal polyps (NPs) are multifactorial soft growths inside the nasal passages and are associated with chronic inflammation that originate from the nasal and paranasal sinus mucosae. This study focused on the role of microRNA (miR)-125b and the molecules associated with NP development. Differentially expressed miRNAs between nasal tissues from patients with chronic rhinosinusitis (CRS) with NP (CRSwNP) and CRS without NP (CRSsNP) were screened using microarray analysis. A murine model of CRSwNP was established. The expression of miR-125b in murine tissues was examined using reverse transcription quantitative polymerase chain reaction. Candidate upstream regulators of miR-125b were predicted using bioinformatics tools, and the binding relationship between specificity protein 1 (Sp1) and miR-125b was validated using luciferase and chromatin immunoprecipitation assays. Altered expression of Sp1 and miR-125b was induced to evaluate their relevance to the progression of NPs. miR-125b expression was significantly upregulated in NP tissues from patients with CRSwNP. Sp1 was confirmed as an upstream regulator that promotes miR-125b transcription in NPs. Overexpression of Sp1 reduced levels of d-dimer (an indicator of fibrinogen degradation products) and tissue-type plasminogen activator (t-PA) but increased eosinophil cationic protein and peroxidase levels, as well as the levels of inflammatory factors interleukin-5 (IL-5) and IL-8 in murine NP tissues. However, these trends were reversed after miR-125b downregulation. Sp1 and miR-125b were found to activate the Wnt/β-catenin signaling pathway in NPs. This study demonstrated that Sp1, an upstream transcription factor of miR-125b, accumulates on the miR-125b promoter to activate its transcription, which induces inflammation and fibrin deposition in NP by activating the Wnt/β-catenin axis.

Expression profiles of hsa-miR-148a-3p and hsa-miR-125b-5p in human breast milk and infant formulae

BackgroundMilk-derived microRNAs (miRNAs), including hsa-miR-148a-3p (miR-148a) and hsa-miR-125b-5p (miR-125b), have been shown to be beneficial to the gastrointestinal function in infants. Here, we investigated their expression during lactation in humans and determined whether the infant formulae available in Japan contain these miRNAs.MethodsHealthy Japanese women (n = 16) who gave birth vaginally or by cesarean section at the Teine Keijinkai Hospital between 1 September 2020, and 31 April 2021 were included in this study. Breast milk was collected by nurses on days 4 or 5 after delivery (hereinafter, transition milk) and on day 30 of postpartum (hereinafter, mature milk). The levels of miR-148a and miR-125b in breastmilk and six commercially available infant formulae were compared and evaluated using quantitative reverse transcription-polymerase chain reaction.ResultsIn all participants, the miR-148a level in mature breastmilk was significantly lower than that in the transition milk. The changes in miR-125b expression during lactation showed similar trends to the changes in miR-148a expression. The miR-148a and miR-125b levels in all analyzed infant formulae were lower than 1/500th and 1/100th of those in mature breastmilk, respectively.ConclusionsThe levels of both miR-148a and miR-125b in human breast milk decreased on day 30 postpartum compared with those in the transition milk. Additionally, the expression of these miRNAs in infant formulae available in Japan was very low. Further studies with larger populations are required to understand precisely the lactational changes in the expression of miR148a and miR-125b in breast milk.

Changes in Serum LncRNA MEG3/miR-181b and UCH-L1 Levels in Patients with Moderate and Severe Intracerebral Hemorrhage.

To study on the association of lnc-MEG3/miR-181b and UCH-L1 in the progression of cerebral hemorrhage. Further facilitation the development of novel strategies that use their potential as a therapeutic targets. In this study, we studied the lncRNA MEG3 and miR-181b expression in 30 patients with ICH who were admitted to the General Hospital of Xinjiang Military Command from January 2021 to May 2021 by quantitative polymerase chain reaction. Serum levels of UCH-L1 were detected by enzyme-linked immune sorbent assay, and disease severity was evaluated using the Glasgow Coma Scale. We also recorded ICH-related deaths in hospital. We found that lnc-MEG3 and UCH-L1 levels increased and miR-181b levels decreased in the serum of patients with ICH. lnc-MEG3, miR-181b, and UCH-L1 levels were also associated with the severity of the condition. Our data indicated that lnc-MEG3, miR-181b, and UCH-L1 are likely involved in the pathophysiology of ICH, and could form the basis of future studies on potential targets for the treatment of traumatic CNS injuries. UCH-L1 could also find application in ICH management. Further studies on the plasma lncRNA-MEG3, miR-181b, and UCH-L1 levels in patients with ICH could yield novel biological targets for the prediction and treatment of ICH.

Apoptosis Induction of Ganoderic Acid-A by Downregulating miR- 125b and miR-365a-3p in Nalm-6 cells

Acute lymphoblastic leukemia is the most common leukemia in children, which is associated with a high relapse rate despite prevalent therapies. Ganoderic acid-A (GAA) is one of the bioactive compounds of Ganoderma lucidum, which possesses potential antileukemic properties. This study aimed to investigate the effect of the GAA extract on the expression of microRNA and the apoptosis induction in the BCP-ALL cell line. In this case-control study, NALM-6 Cells were treated with the GAA extract and L-asparaginase separately. The cell viability and apoptosis rates were examined using MTT and flow cytometry, respectively. Moreover, the effect of the GAA on the expression of miR-125b and miR-365a-3p, in comparison to L-asparaginase, was studied using RT-PCR. The GAA extract inhibited the cell growth in a dose- and time-dependent manner. Moreover, the GAA extract significantly induced apoptosis compared to L-asparaginase (P=0.0021 vs. P=0.0112). The results showed that the treatment of Nalm-6 cells with GAA significantly reduced the expression of miR-125b (P&lt; 0.0001) and miR-365a-3p (P= 0.0001). Furthermore, it was demonstrated that the downregulation of miR-125b and miR-365a-3p was surprisingly higher in the GA-treated Nalm-6 cells than in L-asparaginase-treated Nalm-6 cells. According to the findings, the GAA extract has antileukemic effects and can be used as a promising agent with fewer side effects in all treatments.

MiR-181b promotes the oncogenesis of renal cell carcinoma by targeting TIMP3

Renal cell carcinoma (RCC) has a poor prognosis due to limited diagnosis and treatment. Thus, it is necessary to find novel prognostic biomarkers and therapeutic targets. The aberrant expression of microRNAs plays an important role in RCC oncogenesis. Tissue inhibitors of metalloproteinase 3 (TIMP3) acts as a downstream target of miR-181b. The aim of this study was to understand the role and molecular mechanism of miR-181b in RCC oncogenesis. The results showed that miR-181b expression was significantly higher in RCC tumour tissues, especially in those with significant invasion or metastasis. miR-181b overexpression promoted proliferation and migration of the RCC cell line 786-O, while miR-181b knockdown had the opposite effect. In addition, miR-181b was inversely correlated with TIMP3 expression in RCC tumour tissues. miR-181b overexpression reduced TIMP3 expression in RCC cell line 786-O or OS-RC-2, while miR-181b knockdown had the inverse effect. Mechanistically, a luciferase reporter assay confirmed the binding sites of miR-181b on the 3’-UTR of TIMP3, confirming the targeting effect of miR-181b on TIMP3. Overall, miR-181b promotes the development and progression of RCC by targeting TIMP3 expression, indicating the potential use of miR-181b in the diagnosis and treatment of RCC.

MiR-21, miR-125b, and let-7b contribute to the involution of atretic follicles and corpus lutea in Tibetan sheep ovaries.

Follicular granulosa cells (FGCs) are crucial for ovarian follicle functions, and miRNAs are differentially expressed at various stages of follicular developments. In this study, we confirmed that miR-21, miR-125b, and let-7b were located in FGCs/luteal cells by in situ hybridization experiments. Moreover, miR-21 and miR-125b expressions were upregulated in late corpus lutea (CL) and atretic follicles (AF); let-7b expression was increased in early AF. After transfected with inhibitor or mimic of miRNAs in FGCs, we found that FGCs apoptosis was decreased in the miR-21-mi group but increased in the miR-125b-mi group using flow cytometry. mRNA and protein expression levels were determined for apoptosis-related factors (e.g., Bcl-2 and Bax), the potential target genes of miRNAs (e.g., SMAD7, SP1, and STAT3), hormone receptors (e.g., FSHR and LHR), and genes related to hormone secretion (e.g., CYP19, CYP11, and 3βHSD). The protein levels of SMAD7 were decreased in the miR-21-mi group but opposite to SP1 and FSHR. In the let-7b-mi group, Bcl-2, SMAD7, and FSHR were suppressed but not Bax, CYP11, and 3βHSD. However, hormone secretion was not changed in the supernatant of transfected FGCs. This study provides information about ovarian miRNAs to improve the fertility in Tibetan sheep.

Exosomes derived from bone marrow mesenchymal stem cells inhibit neuroinflammation after traumatic brain injury.

Exosomes derived from bone marrow mesenchymal stem cells can inhibit neuroinflammation through regulating microglial phenotypes and promoting nerve injury repair. However, the underlying molecular mechanism remains unclear. In this study, we investigated the mechanism by which exosomes derived from bone marrow mesenchymal stem cells inhibit neuroinflammation. Our in vitro co-culture experiments showed that bone marrow mesenchymal stem cells and their exosomes promoted the polarization of activated BV2 microglia to their anti-inflammatory phenotype, inhibited the expression of proinflammatory cytokines, and increased the expression of anti-inflammatory cytokines. Our in vivo experiments showed that tail vein injection of exosomes reduced cell apoptosis in cortical tissue of mouse models of traumatic brain injury, inhibited neuroinflammation, and promoted the transformation of microglia to the anti-inflammatory phenotype. We screened some microRNAs related to neuroinflammation using microRNA sequencing and found that microRNA-181b seemed to be actively involved in the process. Finally, we regulated the expression of miR181b in the brain tissue of mouse models of traumatic brain injury using lentiviral transfection. We found that miR181b overexpression effectively reduced apoptosis and neuroinflamatory response after traumatic brain injury and promoted the transformation of microglia to the anti-inflammatory phenotype. The interleukin 10/STAT3 pathway was activated during this process. These findings suggest that the inhibitory effects of exosomes derived from bone marrow mesenchymal stem cells on neuroinflamation after traumatic brain injury may be realized by the action of miR181b on the interleukin 10/STAT3 pathway.