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Background: MicroRNA-150 (miR-150) plays a critical role in immune regulation and has been implicated in autoimmune diseases like Multiple Sclerosis (MS). This review aims to evaluate miR-150's potential as a biomarker for MS, necessitating this review to consolidate current evidence and highlight miR-150's utility in improving diagnostic accuracy and monitoring disease progression. Methods: A comprehensive literature search was conducted in databases like PubMed, Scopus, Google Scholar, SciSpace, MDPI and Web of Science, adhering to PRISMA guidelines. Studies focusing on miR-150 implications in MS were included. Data extraction was conducted, while quality assessment was done using the NOS and AMSTAR 2 tools. With the extracted data a statistical analyses conducted. Results: 10 eligible articles were included in review. Findings show that miR-150 levels were consistently deregulated in MS patients compared to healthy controls, correlating with disease severity and clinical parameters such as (EDSS) scores and disease activity. Additionally, miR-150 is implicated in the inflammatory pathogenesis of MS, affecting immune cell regulation and inflammatory pathways. Conclusions: MiR-150 is a promising biomarker for MS, showing significant potential for improving diagnostic accuracy and monitoring disease progression. Its consistent deregulation in MS patients and correlation with clinical parameters underscore its clinical utility. Further research should validate miR-150's salivary presence and its possible usage as a novel biomarker and therapeutic potential in the development of MS. [ABSTRACT FROM AUTHOR]

Background: One form of cancer that affects the bone marrow and blood is called acute myeloid leukemia (AML). It is distinguished by the myeloblasts, or aberrant white blood cells, growing quickly and interfering with the formation of healthy blood cells. The small non-coding RNA molecule known as microRNA-150 (miR-150) is involved in the control of gene expression in several biological functions, including hematopoiesis, the process that creates new blood cells. miR-150 has been studied in relation to acute AML for its possible functions in leukemogenesis and normal hematopoiesis. Objective: assess the gene expression miRNA150 in AML patients. Materials and methods: In this study, 35 patients aged between 15 to 95 years old in the pre-and post-treatment cohorts and 35 healthy volunteers were included. The samples were obtained from Medical City's Baghdad Teaching Hospital. Results: The age group of AML patients did not significantly differ from the control group (P≥0.05). The expression of the miR-150 gene was downregulated in the untreated AML patients while it was upregulated in the treated AML patients in comparison with the healthy control group.Conclusions: The analysis indicated that there was no significant difference in the age distribution between patients infected with Acute myeloid leukemia and the control group. miR-150 expression was downregulated in untreated AML patients while it was upregulated in treated AML patients. Consequently, miR-150 might be regarded as an AML prognostic marker.

AIM: To investigate the mechanism by which NF-κB p65 activates miR-150 to suppress TRPC6 expression and promote renal ischemia-reperfusion injury. METHODS: To assess the transcription of miR-150, NF-B p65, and TRPC6 in HK-2 cells treated with hypoxia reperfusion and rat kidney tissue damaged by ischemia-reperfusion (I/R), qPCR was implemented. The protein production of NF-κB p65 and TRPC6 was assessed by Western blot (WB) analysis. The histological score of rat kidney tissue was assessed using H&E (hematoxylin and eosin) staining. To assess the rate of apoptosis of renal tissue cells following I/R injury, we used the TACS TdT In Situ Apoptosis Detection Kit. To find out the impairment of renal function, blood levels of creatinine (Cr) and blood urea nitrogen (BUN) were tested in rats. Concentrations of inflammatory cytokines, including IL-1β, IL-10, and TNF-α, were detected in HK-2 cells and rat renal tissue cells utilizing ELISA kits. FITC and CCK-8 were employed to analyze the death rate and cellular proliferation of HK-2 cells. To analyse the mechanism of engagement between NF-κB p65 and the miR-150 promoter, coupled with the detrimental impact of miR-150 on TRPC6, we adopted the dual-luciferase reporter assay. To confirm the activating effect of NF-κB p65 on miR-150,we implemented the ChIP assay. RESULTS: NF-κB p65 expression was significantly upregulated in rat renal tissue following IRI. Applying the dual-luciferase reporter assay, we demonstrated that the specific attachment of NF-B p65 with the miR-150 promoter location is viable, resulting in the promotion of the activity of the promoter. When miR-150 was overexpressed, we observed a notable reduction in cell proliferation. And it notably increased the rate of cellular apoptosis rate and amounts of the proinflammatory cytokines IL-1β, IL-10, and TNF-α. Employing the dual-luciferase reporter assay, we demonstrated that miR-150 transfection diminished the function of luciferase in the TRPC6-WT group, whereas luciferase activity in the TRPC6-MUT group remained unchanged, indicating that miR-150 is a targeted inhibitor of TRPC6. In the rat renal I/R model, when miR-150 was inhibited or TRPC6 was overexpressed in the rat kidney I/R model, the histological score of rat kidney tissue significantly decreased, so did the quantities of proinflammatory cytokines IL-1β, IL-10, TNF-α, creatinine (Cr) and blood urea nitrogen (BUN) contents and the rate of cell apoptosis in kidney tissue. CONCLUSION: Activation of miR-150 by NF-κB p65 results in downregulation of TRPC6 expression and promotion of IRI in the kidney. [ABSTRACT FROM AUTHOR]

Abstract There is a growing interest to understand the role and mechanism of action of microRNAs (miRNAs) in cancer. The miRNAs are defined as short non-coding RNAs (18-22nt) that regulate fundamental cellular processes through mRNA targeting in multicellular organisms. The miR-150 is one of the miRNAs that have a crucial role during tumor cell progression and metastasis. Based on accumulated evidence, miR-150 acts as a double-edged sword in malignant cells, leading to either tumor-suppressive or oncogenic function. An overview of miR-150 function and interactions with regulatory and signaling pathways helps to elucidate these inconsistent effects in metastatic cells. Aberrant levels of miR-150 are detectable in metastatic cells that are closely related to cancer cell migration, invasion, and angiogenesis. The ability of miR-150 in regulating of epithelial-mesenchymal transition (EMT) process, a critical stage in tumor cell migration and metastasis, has been highlighted. Depending on the cancer cells type and gene expression profile, levels of miR-150 and potential target genes in the fundamental cellular process can be different. Interaction between miR-150 and other non-coding RNAs, such as long non-coding RNAs and circular RNAs, can have a profound effect on the behavior of metastatic cells. MiR-150 plays a significant role in cancer metastasis and may be a potential therapeutic target for preventing or treating metastatic cancer.

Objective: To investigate the effects of miR-150 on expression of PD-1 in peripheral T cells and lung tumor growth in mice. Methods: miR-150 gene knockout (miR-150KO) and wild-type normal control (WT) mice were selected, number changes of peripheral T cells,expression of activated phenotype molecule CD69, and immune checkpoint molecule PD-1 were detected by flow cytometry. Lewis lung cancer cell line (LLC) was used to prepare transplanted tumor models in miR-150KO and WT mice by subcutaneous injection, and effect of miR-150 on growth of lung tumor was observed. Anti-PD-1 antibody was used to intraperitoneally inject miR-150KO and WT tumor-bearing mice, and its effect on tumor growth inhibition was observed. Results: Compared with WT mice, proportion and number of CD4+T cells in lymph nodes and spleen of miR-150KO mice were significantly increased, while proportion and number of CD4+T and CD8+T cells in peripheral blood were significantly decreased. miR-150 knockout resulted in a significant increase in proportion of CD69+ cells in CD4 T and CD8 T cells of lymph nodes and peripheral blood, as well as a significant increase in proportion of PD-1+ cells in CD4 T and CD8 T cells of peripheral blood. Compared with WT tumor-bearing mice, tumor growth was significantly accelerated in miR-150KO tumor-bearing mice, and proportion of PD-1+ cells in CD4 T and CD8 T cells in peripheral blood and lymph nodes of miR-150KO tumor-bearing mice was also significantly increased. Anti-PD-1 antibody treatment significantly inhibited tumor growth of miR-150KO tumor-bearing mice. Conclusion: miR-150 knockout promotes the growth of transplanted lung tumor in mice by increasing expression of PD-1 in T cells, but also enhances the immunosuppressive effect of anti-PD-1 antibody on tumor. [ABSTRACT FROM AUTHOR]

Wogonin, an active constituent of Scutellaria baicalensis Georgi, exhibits antitumor potential. This study aimed to study the effect and mechanism of wogonin on the apoptosis and proliferation of nasopharyngeal carcinoma cells. Methyl thiazolyl tetrazolium-based cell viability, flow cytometry, and Transwell assays were conducted to assess the cells' malignant behaviors, and western blot was utilized to assess protein expression. The results indicated that wogonin inhibited nasopharyngeal carcinoma cell proliferation, migration, invasion, and elevated cell apoptosis in a dose-dependent way. Besides, wogonin inhibited miR-150 expression in nasopharyngeal carcinoma cells in a dose-dependent way. After transfection with a miR-150 inhibitor, the proliferation, migration, and invasion of nasopharyngeal carcinoma cells were hindered, while the apoptosis rate was enhanced. Moreover, miR-150 reduction increased phosphatase and tensin homolog expression while decreasing p-Akt expression in cells. Rescue assays further validated that phosphatase and tensin homolog silencers reversed the impacts of miR-150 downregulation on nasopharyngeal carcinoma cells malignant behaviors, and miR-150 elevation reversed the impacts of wogonin on nasopharyngeal carcinoma cells' malignant behaviors. To sum up, wogonin inhibited nasopharyngeal carcinoma cell proliferation, migration, and invasion via the miR-150/phosphatase and tensin homolog/Akt axes. [ABSTRACT FROM AUTHOR]

Background: Current studies have suggested that miRNA is beneficial in inhibiting myocardial remodeling after myocardial infarction (AMI), however, its underlying mechanism is unclear. Objectives: We aimed to investigate whether miR-150 can inhibit myocardial remodeling after myocardial infarction and whether this process is regulated by the miR-150/TET3 pathway. Methods: On the first day, C57BL/6 AMI mice(n = 15) were administrated with miR-150, and another 15 AMI mice were administrated with the same volume of control Agomir. Left ventricular ejection fraction (LVEF%) and myocardial remodeling were compared after one week; TET3 (ten-eleven translocation 3) and VEGF-α (vascular endothelial growth factor-α) were also determined in the infracted heart simultaneously. The neovascularization in the infarcted area at day 21 was compared through CD31 using fluorescence microscopy; Activated monocytes stimulated with LPS were transfected with miR-150. Laser scanning confocal microscopy was used to detect the intracytoplasmic imaging of miR-150 in Ly6Chigh monocytes. Expression of the miR-150 in the monocytes was measured using Q-PCR. After 48 h, the proportion of Ly6Chigh/low monocytes was determined using flow cytometry. Expression of TET3 in Ly6Chigh/low monocytes was measured using Q-PCR and Western blot. After the downregulation of TET3 specifically, the levels of Ly6Chigh/low monocytes were further determined. Results: We first observed an increased trend of mice survival rate in the miR-150 injection group, but it didn't reach a statistical difference (66.7% vs. 40.0%, p = 0.272). However, AMI mice administrated with miR-150 displayed better LVEF% (51.78%±2.90% vs. 40.28%±4.20%, p<0.001) and decreased infarct size% (25.47 ± 7.75 vs. 50.39 ± 16.91, p = 0.002). After miR-150 was transfected into monocytes, the percentage of Ly6Clow monocytes increased significantly after 48 h (48.5%±10.1% vs. 42.5%±8.3%, p < 0.001). Finally, Western blot analysis (0.56 ± 0.10/β-actin vs. 0.99 ± 0.12/β-actin, p < 0.001) and real-time PCR (1.09 ± 0.09/GAPDH vs. 2.53 ± 0.15/GAPDH, p < 0.001, p < 0.001) both confirmed decreased expression of TET3 in monocytes after transfection with miR-150. After the downregulation of TET3 specifically, Ly6Clow monocytes showed a significant increase (16.73%±6.45% vs. 6.94%±2.99%, p<0.001, p < 0.001). Conclusions: miR-150 alleviated myocardial remodeling after AMI. Possible mechanisms are ascribed to the regulating of TET3 and VEGF-α in inflammatory monocytes. [ABSTRACT FROM AUTHOR]

Granulosa cells (GCs) proliferation and apoptosis play a significantly role in follicular development and atresia. ID1 and miR-150 are involved in cell apoptosis and follicular atresia, but the interaction and function of ID1 and miR-150 in GCs are unclear. This study focuses on ID1 and miR-150 in terms of the interaction and effects on proliferation and apoptosis in ovine granulosa cells. Our findings revealed that ID1 decreased the promoter activity and expression level of oar-miR-150. However, the expression of ID1 was downregulated by miR-150, and ID1 was identified as a target gene of oar-miR-150. miR-150 mimic inhibited proliferation and upregulated apoptosis rate in ovine GCs, while the results of miR-150 inhibitor were opposite. Overexpression of ID1 significantly inhibited ovine GCs proliferation and cell cycle-related genes (CDK1 , CDK2 , CDK4 , CCND2 , CDC20 , and PCNA) expression, whereas knockdown of ID1 promoted cell proliferation and those genes expression. Overexpression of ID1 significantly downregulated mitochondrial membrane potential and Bcl-2 expression in ovine GCs, and upregulated the expression of pro-apoptosis genes Bax , Caspase-3 , and Caspase-9 , whereas the results of ID1 knockdown were reversed. Collectively, these findings indicate the interaction and the vital role of ID1 and miR-150 on proliferation and apoptosis in ovine granulosa cells, which may suggest a novel target for ovine follicular development and atresia. • ID1, as a transcription factor, represses the transcription of miR-150 in ovine granulosa cells. • ID1 , as a mRNA, is a target gene of oar-miR-150. • ID1 inhibits proliferation and promotes apoptosis of ovine granulosa cells. [ABSTRACT FROM AUTHOR]

Objective To investigate the role of long non-coding RNA family with sequence similarity 83 member A antisense RNA 1 in retinoblastoma （RB） cells and its potential molecular mechanism. Methods RB cells were cultured in vitro, and Vector, pcDNA-FAM83A-AS1, NC-siRNA, and FAM83A-AS1-siRNA were transfected into cells to detect the expression of FAM83A-AS1, RB cell proliferation ability, and apoptosis rate in RB cells. Bioinformatics and dual-luciferase reporter gene experiments were performed to predict and verify the targeting relationship between FAM83A-AS1 and miR-150, and miR-150 and the high-mobility family protein A2 （HMGA 2）. The expression of miR-150 and HMGA2 mRNA in RB cells was measured by RT-qPCR； HMGA 2 protein in RB cells by Western blot； and the proliferation and apoptotic capacity of RB cells after transfection by MTT assay and flow cytometry. Results The expression of FAM83A-AS1 in the pcDNA-FAM83A-AS1 group was significantly higher than that of the Vector group and lower than that of the NC-siRNA group （P < 0.05）. The cell proliferation capacity in the pcDNA-FAM83A-AS1 group was significantly higher, and the apoptosis rate was significantly lower （P < 0.05）. Compared with NC-siRNA group, FAM83A-AS1-siRNA group showed significantly increased apoptosis rate （P < 0.05）. The miR-150 mimic significantly inhibited the proliferation capacity of RB cells and promoted cell apoptosis. However, pcDNA-HMGA 2 significantly reversed the effect of miR-150 mimic on the proliferation and apoptosis of RB cells. Conclusion Knockdown of lncRNA FAM83A-AS1 inhibited RB cell proliferation and promoted apoptosis by regulating the miR-150/HMGA2 axis. [ABSTRACT FROM AUTHOR]

There is a growing interest to understand the role and mechanism of action of microRNAs (miRNAs) in cancer. The miRNAs are defined as short non-coding RNAs (18-22nt) that regulate fundamental cellular processes through mRNA targeting in multicellular organisms. The miR-150 is one of the miRNAs that have a crucial role during tumor cell progression and metastasis. Based on accumulated evidence, miR-150 acts as a double-edged sword in malignant cells, leading to either tumor-suppressive or oncogenic function. An overview of miR-150 function and interactions with regulatory and signaling pathways helps to elucidate these inconsistent effects in metastatic cells. Aberrant levels of miR-150 are detectable in metastatic cells that are closely related to cancer cell migration, invasion, and angiogenesis. The ability of miR-150 in regulating of epithelial-mesenchymal transition (EMT) process, a critical stage in tumor cell migration and metastasis, has been highlighted. Depending on the cancer cells type and gene expression profile, levels of miR-150 and potential target genes in the fundamental cellular process can be different. Interaction between miR-150 and other non-coding RNAs, such as long non-coding RNAs and circular RNAs, can have a profound effect on the behavior of metastatic cells. MiR-150 plays a significant role in cancer metastasis and may be a potential therapeutic target for preventing or treating metastatic cancer. [ABSTRACT FROM AUTHOR]

Objective To investigate the relationship between the expression of CXC chemokine ligand 8 (CXCL8) and miR-150 in the skin lesions of patients with psoriasis vulgaris and the severity of the disease. Methods The skin lesions of 80 patients with psoriasis vulgaris who were treated in Nanyang first people's Hospital from January 2020 to May 2021 were selected as the research objects. The normal tissues around the skin lesion were chosen as a control. The Psoriasis Area and Severity Index (PASI) was used to classify patients with psoriasis, the immunohistochemical method was used to detect the expression of CXCL8 protein, the real time fluorescence quantitative PCR method was used to detect the expression of miR-150, Western blot was used to detect the expression of CXCL8 protein, and the correlation between the expression levels of CXCL8 protein, miR-150 and the severity of the disease was further analyzed. Results The level of CXCL8 mRNA in the skin lesion of patients with psoriasis vulgaris was higher than that in normal tissues (P＜0.05) and the level of miR-150 was lower than that in normal tissues(P＜0.05). The expression of CXCL8 protein in the skin lesions of patients was 68.75%, which was significantly higher than 37.50% in normal tissues (P＜0.05); the expression of CXCL8 protein in the skin lesions of patients was significantly higher than that in normal tissues (P＜0.05); the level of miR-150 gradually decreased with the aggravation of the disease (P＜0.05), and the level of CXCL8 protein gradually increased with the aggravation of the disease (P＜0.05); Pearson results showed that there was a negative correlation between miR-150 level in patients with psoriasis vulgaris and CXCL8 protein level and PASI score (r=-0.467, -0.475, P＜0.05), and there was a positive correlation between CXCL8 protein level and PASI score (r=0.424, P＜0.05). Conclusions The expression of miR-150 decreased and CXCL8 increased in patients with psoriasis vulgaris, both of them were related to the severity of the disease.

Background and Aims: To examine the roles of microRNAs in the development of colitis, we conducted the RNA-sequencing studies using RNA derived from normal and colitogenic CD4+ T cells. Colitogenic CD4+ T cells demonstrated the increased expression of miR-150. We focused on the involvement of miR-150 in the colitis. Methods: We crossed miR-150 knockout mice and T-cell–specific Rap1KO mice, which is colitis model mice and spontaneously develop the colitis with tubular adenomas in microbiota-dependent manner. Results: MiR-150 silencing completely inhibited the expansion of pathogenic Th17 cells and the development of colitis. Conclusion: MiR-150 is a potential therapeutic target of inflammatory bowel diseases.

MicroRNAs (miRNAs) play vital roles in the post-transcriptional regulation of gene expression. Previous studies have shown that miR-150 is a crucial regulator of B cell proliferation, differentiation, metabolism, and apoptosis. miR-150 regulates the immune homeostasis during the development of obesity and is aberrantly expressed in multiple B-cell-related malignant tumors. Additionally, the altered expression of MIR-150 is a diagnostic biomarker of various autoimmune diseases. Furthermore, exosome-derived miR-150 is considered as prognostic tool in B cell lymphoma, autoimmune diseases and immune-mediated disorders, suggesting miR-150 plays a vital role in disease onset and progression. In this review, we summarized the miR-150-dependent regulation of B cell function in B cell-related immune diseases. [ABSTRACT FROM AUTHOR]

RNA guanine quadruplexes (G4s) regulate RNA functions, metabolism, and processing. G4s formed within precursors of microRNAs (pre-miRNAs) may impair pre-miRNAs maturation by Dicer, thus repressing mature miRNA biogenesis. As miRNAs are essential for proper embryonic development, we studied the role of G4s on miRNA biogenesis in vivo during zebrafish embryogenesis. We performed a computational analysis on zebrafish pre-miRNAs to find putative G4 forming sequences (PQSs). The precursor of the miRNA 150 (pre-miR-150) was found to contain an evolutionarily conserved PQS formed by three G-tetrads and able to fold in vitro as G4. MiR-150 controls the expression of myb, which shows a well-defined knock-down phenotype in zebrafish developing embryos. We microinjected zebrafish embryos with in vitro transcribed pre-miR-150 synthesized using either GTP (G-pre-miR-150) or 7-Deaza-GTP, a GTP analogue unable to form G4s (7DG-pre-miR-150). Compared to embryos injected with G-pre-miR-150, embryos injected with 7DG-pre-miR-150 showed higher levels of miRNA 150 (miR-150) and lower levels of myb mRNA and stronger phenotypes associated with myb knock-down. The incubation of pre-miR-150 prior to the injection with the G4 stabilizing ligand pyridostatin (PDS) reverted gene expression variations and rescued the phenotypes related to myb knock-down. Overall, results suggest that the G4 formed in pre-miR-150 functions in vivo as a conserved regulatory structure competing with the stem-loop structure necessary for miRNA biogenesis. [ABSTRACT FROM AUTHOR]

MicroRNA-150 (miR-150) has been shown to play a general role in the immune system, but very little is known about its role on CD4+ T cell responses. During T cell responses against superantigen Staphylococcal Enterotoxin A, miR-150 expression was down-regulated in antigen-specific CD4+ T cells but upregulated in CD8+ T cells. CD4+ and CD8+ T cell clonal expansion was greater in miR-150-KO mice than in WT mice, but miR-150 selectively repressed IL-2 production in CD4+ T cells. Transcriptome analysis of CD4+ T cells demonstrated that apoptosis and mTOR pathways were highly enriched in the absence of miR-150. Mechanistic studies confirmed that miR-150 promoted apoptosis specifically in antigen-specific CD4+ T cells, but not in bystander CD4+ nor in CD8+ T cells. Furthermore, inhibition of mTOR-linked mitochondrial superoxidedismutase-2 increased apoptosis in miR-150-/- antigen-specific CD4+ T. Thus, miR-150 impacts CD4+ T cell helper activity by attenuating IL-2 production along with clonal expansion, and suppresses superoxidedismutase to promote apoptosis. [ABSTRACT FROM AUTHOR]

Objective To analyze differential expression of long non-coding RNA (lncRNA) after miR-150 over-expression by human renal tubular epithelial cell line HK-2 and explore the role of miR-150 in renal tubular injury through regulating the expression of lncRNA. Methods HK-2 cells with miR-150 mimic and scramble were sequenced by Illumina NovaSeq 6000 sequencer. The differentially expressed lncRNA expression profile, GO analysis and KEGG analysis were performed to verify miR-150-lncRNA-JAK2-STAT1/3-COL1 pathway. Results Compared with the scramble group, 362 differential expression lncRNAs were detected in miR-150 mimic group, of which, 252 lncRNAs were down-regulated and 110 lncRNAs were up-regulated both more than 1.5-fold. The results showed that the miR-150 regulated lncRNA and function in biological process, cell components and molecular mechanisms through enrichment analysis of KEGG pathway, miR-150-lncRNA-JAK2-STAT1/3-COL1 pathway was found and then verified by Western blot. Conclusions LncRNAs regulated by miR-150 may play some roles in pathogenesis and molecular mechanisms in human renal tubular injury.

Rationale: Lung cancer is the leading cause of cancer death worldwide, and treatment options are limited to mainly cytotoxic agents. Here we reveal a novel role of miR-150 in non-small cell lung cancer (NSCLC) development and seek potential new therapeutic targets. Methods: The miR-150-mediated autophagy dysfunction in NSCLC cells were examined using molecular methods in vitro and in vivo. The upstream regulatory element and downstream target of miR-150 were identified in vitro and validated in vivo. Potential therapeutic methods (anti-c-myc or anti-miR-150) were tested in vitro and in vivo. Clinical relevance of the c-myc/miR-150/EPG5 axis in NSCLC was validated in human clinical samples and large genomics database. Results: miR-150 blocked the fusion of autophagosomes and lysosomes through directly repressing EPG5. The miR-150-mediated autophagy defect induced ER stress and increased cellular ROS levels and DNA damage response, and promoted NSCLC cell proliferation and tumor growth. Knockdown of EPG5 promoted NSCLC cell proliferation, and attenuated the effects of miR-150. c-myc gene was identified as a miR-150 transcriptional factor which increased miR-150 accumulation, therefore pharmacologically or genetically inhibiting c-myc/miR-150 expression significantly inhibited NSCLC cell growth in vitro and in vivo. Both c-myc and miR-150 were significantly over-expressed in NSCLC, while EPG5 was down-regulated in NSCLC. Expression levels of these molecules were well correlated, and also well correlated with patient survival. Conclusions: Our findings suggest that c-myc/miR-150/EPG5 mediated dysfunction of autophagy contributes to NSCLC development, which may provide a potential new diagnostic and therapeutic target in NSCLC.

Cirrhosis and hepatocellular carcinoma (HCC) are related to chronic liver diseases. Diagnostic algorithms are needed to discriminate HCC from cirrhosis for better patient management. This study aimed to determine the potential of miR-122 and miR-150 to differentiate HCC from liver cirrhosis. This study used a cross-sectional method involving 66 patients with liver cirrhosis, 27 subjects with HCC, and 29 healthy controls. Examination of miR-122 and miR-150 levels from blood plasma used real-time quantitative polymerase chain reaction and their relative expressions were calculated. Clinical and laboratory data were collected and graphed for the Area Under the Curve (AUC) and also for comparison using unpaired T-tests, Kruskal-Wallis, Mann-Whitney, and Chi-square tests with significance set as p

Adipose-derived mesenchymal stem cells (ADSCs) are multipotent stromal cells and play huge role in forming and repairing bone tissues. Emerging evidence shows that MicroRNAs (miRNAs) are involved in ADSCs differentiation. Here, we explored the role of miR-150-5p and its related mechanisms in ADSCs osteogenesis. Real-time PCR was used to determine miR-150-5p expression during ADSCs osteogenesis. miR-150-5p inhibitors, miR-150-5p ADV or short hairpin RNA (shRNA) of Notch3 were transfected to ADSCs for analyzing the effects on osteogenesis. The mixture of hydroxyapatite/tricalcium phosphate (HA/TCP) ceramic powders and transfected ADSCs was implanted into BALB/C nude mice. Micro-CT and histological methods were performed to evaluate the new bone formation. Compared with negative control (NC) and miR-150-5p overexpression, inhibition of miR-150-5p increased ADSCs osteogenesis by regulating Notch3. MiR-150-5p overexpression decreased the expression of pFAK, pERK1/2, and RhoA, while these were up-regulated when miR-150-5p was inhibited, or notch3 was silenced. Furthermore, miR-150-5p inhibition partially reversed the suppression effect of notch3 knockdown on osteogenesis in vitro and in vivo. This study demonstrated the critical function of miR-150-5p during osteogenesis. The combination of ADSCs with miR-150-5p inhibition and HA/TCP might be a promising strategy for bone damage repair. Osteoporosis is a common chronic metabolic bone disease in humans. Bone tissue engineering based on mesenchymal stem cells, biomaterials, and growth factors, provides a promising way to treat osteoporosis and bone defects. ADSCs commonly differentiate into adipose cells, they can also differentiate into osteogenic cell lineages. Nucleic acids and protein have usually been considered as regulators of ADSCs osteogenic differentiation. In the current study, we demonstrated the combination of ADSCs with miR-150-5p inhibition and hydroxyapatite/tricalcium phosphate ceramic powders enhanced bone regeneration. Furthermore, miR-150-5p /Notch3 axis regulating osteogenesis via the FAK/ERK1/2 and RhoA pathway was assessed. The current study showed the application of ADSCs in bone regeneration might be a promising strategy for osteoporosis and bone damage repairing. [Display omitted] [ABSTRACT FROM AUTHOR]

Identification of biomarkers is crucial in guiding the treatment decision and improving the future outcomes of DLBCL. The aim of the current study is to detect the biochemical and clinical impacts of miR-150 and miR-21 expression levels in DLBCL. Quantification of serum miR-150 and miR-21 expression levels by real-time PCR after micro-RNA extraction and RT-PCR. At a cutoff point of 2.3 for miR-21, the sensitivity, specificity, positive predictive, and negative predictive values for diagnosis of DLBCL were 98%, 90%, 90.7%, and 97.8%, respectively. At cut-off point (≤19.12) the sensitivity, specificity, the positive predictive and negative predictive values of miR-21 to discriminate stage IV vs stage II DLBCL patients were 68.42%, 80%, 86.7%%,and 57.1%, respectively. Serum miR-150 and serum miR-21 can be used as diagnostic markers for DLBCL patients, but miR-21 is more sensitive than miR-150. Serum miR-21 can be used as prognostic marker for DLBCL patients. It was more sensitive and more specific than miR-150. [ABSTRACT FROM AUTHOR]

MicroRNA-150 (miR-150) has been shown to play a general role in the immune system, but very little is known about its role on CD4+ T cell responses. During T cell responses against superantigen Staphylococcal Enterotoxin A, miR-150 expression was down-regulated in antigen-specific CD4+ T cells but up-regulated in CD8+ T cells. CD4+ and CD8+ T cell clonal expansion was greater in miR-150-KO mice than in WT mice, but miR-150 selectively repressed IL-2 production in CD4+ T cells. Transcriptome analysis of CD4+ T cells demonstrated that apoptosis and mTOR pathways were highly enriched in the absence of miR-150. Mechanistic studies confirmed that miR-150 promoted apoptosis specifically in antigen-specific CD4+ T cells, but not in bystander CD4+ nor in CD8+ T cells. Furthermore, inhibition of mTOR-linked mitochondrial superoxidedismutase-2 increased apoptosis in miR-150-/- antigen-specific CD4+ T. Thus, miR-150 impacts CD4+ T cell helper activity by attenuating IL-2 production along with clonal expansion, and suppresses superoxidedismutase to promote apoptosis.

Aim: The purpose of this study was to investigate the functions of exosomal miR-150 derived from bone marrow mesenchymal stem cells in osteonecrosis of the femoral head (ONFH). Materials & methods: Cell viability and apoptosis were detected using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and flow cytometry. Alizarin red staining was performed to detect calcium deposits. A rat model was established to assess the effects of exosomal miR-150 on ONFH in vivo. Results: Exosomes or exosomal miR-150 derived from bone marrow mesenchymal stem cells inhibited TNF-α-induced osteoblast apoptosis and promoted osteogenic differentiation and autophagy. Exosomal miR-150 suppressed apoptosis and induced autophagy in TNF-α-treated osteoblasts by regulating the GREM1/NF-κB axis. Exosomal miR-150 also improved the pathological features of ONFH in vivo. Conclusion: Exosomal miR-150 alleviates ONFH by mediating the GREM1/NF-κB axis. This study provides a potential therapeutic strategy for ONFH. Osteonecrosis of the femoral head (ONFH) is an orthopedic disease that frequently occurs in young adults aged less than 50 years. At present, there is no widely accepted curative surgical procedure or drug therapy for this disease. Bone marrow mesenchymal stem cells (BMSCs) play a key role in the progression of ONFH. BMSC-derived exosomes refer to small membrane vesicles that can transfer proteins, miRNAs and mRNAs, which are closely related to the development of ONFH. This study showed that exosomal miRNA-150 derived from BMSCs inhibited TNF-α-induced osteoblast apoptosis and promoted osteogenic differentiation and autophagy by regulating the GREM1/NF-κB axis. In addition, exosomal miRNA-150 alleviated the symptoms of ONFH in rats. [ABSTRACT FROM AUTHOR]

Human T-cell leukemia virus-1 (HTLV-1) is a retrovirus that persistently infects CD4+ T-cells, and is the causative agent of adult T-cell leukemia/lymphoma (ATLL), tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM) and several inflammatory diseases. T-cell transformation by HTLV-1 is driven by multiple interactions between viral regulatory proteins and host cell pathways that govern cell proliferation and survival. Studies performed over the last decade have revealed alterations in the expression of many microRNAs in HTLV-1-infected cells and ATLL cells, and have identified several microRNA targets with roles in the viral life cycle and host cell turnover. This review centers on miR-150-5p, a microRNA whose expression is temporally regulated during lymphocyte development and altered in several hematological malignancies. The levels of miR-150-5p are reduced in many HTLV-1-transformed- and ATLL-derived cell lines. Experiments in these cell lines showed that downregulation of miR-150-5p results in activation of the transcription factor STAT1, which is a direct target of the miRNA. However, data on miR-150-5p levels in freshly isolated ATLL samples are suggestive of its upregulation compared to controls. These apparently puzzling findings highlight the need for more in-depth studies of the role of miR-150-5p in HTLV-1 infection and pathogenesis based on knowledge of miR-150-5p-target mRNA interactions and mechanisms regulating its function in normal leukocytes and hematologic neoplasms. [ABSTRACT FROM AUTHOR]

The prognostic characteristics of pancreatic cancer (PC) are determined by the contributing factors from the tumor microenvironment. Leptin is a critical oncogenic factor released by adipocytes as an adipokine into the tumor microenvironment, where it promotes tumor development by activating cancer stem cell (CSC) molecular regulators Notch, Hedgehog, and Wnt/β-catenin signaling. One of the downstream targets of these pathways is CDK4/6 and cyclin D which is controlled by P16 INK4A that is highly mutated in PC. Therefore, the purpose of this study was to determine the effect of a CDK4/6 inhibitor, palbociclib, on Leptin-induced PC cells and to target the Notch, Hedgehog, and Wnt/β-catenin signaling pathways via miR-150, miR-506, and miR-208 modulation. Leptin treatment increased the ability of Panc-1, MiaPaCa-2, and Capan-2 cells to proliferate and decreased the effect of palbociclib. Additionally, tumorspheres were generated from Leptin-treated (Leptin+) and Leptin-untreated (Leptin-) Panc-1 and MiaPaCa-2 cells and transfected with miR-506, miR-150 (tumorsuppressor miRNAs), or anti-miR-208 (oncomiR), followed by palbociclib treatment. Forced expression of miR-506 or miR-150 significantly increased the susceptibility of Leptin+ cells to palbociclib treatment by inhibiting colony and tumor spheroid formation, and CD44 expression in Panc-1 and MiaPaCa-2 cells. Additionally, the increased miR-150 expression is more effective at inhibiting N-cadherin, β-catenin, p-GSK3β, Notch, and Wnt5a/b expression in Leptin-/+ Panc-1 and MiaPaCa-2 cells. As a result, palbociclib suppressed the CSC profile induced by leptin treatment, inhibiting both tumorsphere forms and leptin-targeted signaling pathways, thereby disabling the Panc-1 and MiaPaCa-2 cells' resistance mechanism. Increased expression of miR-506 or miR-150 and inhibition of miR-208 enhanced sensitivity of Panc-1 and MiaPaCa-2 Leptin-/+ cells to palbociclib treatment. As a result, this study proved that combining inhibitors of CSC molecular regulators with palbociclib improves the success rate of inhibition of PC cell proliferation. [ABSTRACT FROM AUTHOR]

Human T-cell leukemia virus-1 (HTLV-1) is a retrovirus that persistently infects CD4+ T-cells, and is the causative agent of adult T-cell leukemia/lymphoma (ATLL), tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM) and several inflammatory diseases. T-cell transformation by HTLV-1 is driven by multiple interactions between viral regulatory proteins and host cell pathways that govern cell proliferation and survival. Studies performed over the last decade have revealed alterations in the expression of many microRNAs in HTLV-1-infected cells and ATLL cells, and have identified several microRNA targets with roles in the viral life cycle and host cell turnover. This review centers on miR-150-5p, a microRNA whose expression is temporally regulated during lymphocyte development and altered in several hematological malignancies. The levels of miR-150-5p are reduced in many HTLV-1-transformed- and ATLL-derived cell lines. Experiments in these cell lines showed that downregulation of miR-150-5p results in activation of the transcription factor STAT1, which is a direct target of the miRNA. However, data on miR-150-5p levels in freshly isolated ATLL samples are suggestive of its upregulation compared to controls. These apparently puzzling findings highlight the need for more in-depth studies of the role of miR-150-5p in HTLV-1 infection and pathogenesis based on knowledge of miR-150-5p-target mRNA interactions and mechanisms regulating its function in normal leukocytes and hematologic neoplasms.

Hosts exploit various approaches to defend against porcine reproductive and respiratory syndrome virus (PRRSV) infection. microRNAs (miRNAs) have emerged as key negative post-transcriptional regulators of gene expression and have been reported to play important roles in regulating virus infection. Here, we identified that miR-150 was differentially expressed in virus permissive and non-permissive cells. Subsequently, we demonstrated that PRRSV induced the expression of miR-150 via activating the protein kinase C (PKC)/c-Jun amino-terminal kinases (JNK)/c-Jun pathway, and overexpression of miR-150 suppressed PRRSV replication. Further analysis revealed that miR-150 not only directly targeted the PRRSV genome, but also facilitated type I IFN signaling. RNA immunoprecipitation assay demonstrated that miR-150 targeted the suppressor of cytokine signaling 1 (SOCS1), which is a negative regulator of Janus activated kinase (JAK)/signal transducer and activator of the transcription (STAT) signaling pathway. The inverse correlation between miR-150 and SOCS1 expression implies that miR-150 plays a role in regulating ISG expression. In conclusion, miR-150 expression is upregulated upon PRRSV infection. miR-150 feedback positively targets the PRRSV genome and promotes type I IFN signaling, which can be seen as a host defensive strategy. [ABSTRACT FROM AUTHOR]

Myocardial reperfusion is an effective therapy for acute myocardial infarction (AMI). However, ischemia/reperfusion (I/R) injury following myocardial reperfusion is a significant limitation for AMI treatment. Five prime to Xist (FTX) was recognized as a biomarker of multiple diseases, including heart disease. However, the molecular mechanism of FTX in I/R injury is unclear.

Abstract Background Deep venous thrombosis (DVT) constitutes a major global disease burden. Endothelial progenitor cells (EPCs) have been described in association with recanalization of venous thrombus. Furthermore, emerging evidence suggests microRNAs are involved in this progression. The goal of this study was to investigate the influence of miR-150 on the behavior of EPCs and its potential contribution in venous thrombosis resolution. Methods We isolated and cultured EPCs from healthy adults. Next, early EPCs or endothelial colony-forming cells (ECFCs or late EPCs) were transfected with miR-150 agomir and antagomir. Gene expression profiles, proliferation, cytokine secretion, and angiogenic capacity of early EPCs and ECFCs were examined. The effects of miR-150 on c-Myb expression and Akt/FOXO1 signaling were also evaluated. Furthermore, a rat model of venous thrombosis was constructed to determine the in vivo function of EPCs. Results Our results showed that miR-150 overexpression in early EPCs significantly promoted differentiation to ECFCs and contributed to proliferation and tube formation. However, suppression of miR-150 in late EPCs inhibited proliferation and tube formation. Moreover, we identified that this progression is regulated by inhibition of c-Myb and activation of the Akt/FOXO1 pathway. Our findings also showed that miR-150 led to the enhanced resolution ability of EPCs in a rat venous thrombosis model. Conclusions In this study, we present a novel mechanism of miRNA-mediated regulation of EPCs and Akt activation in thrombus resolution.

Background: Extracellular vesicles (EV) concentration is generally increased in patients with cardiovascular diseases, although the protective role of EVs in atherosclerosis has been reported. Among the specific cargo of EVs, miRNAs contribute to different stages of atherosclerosis. Aim of the present report has been to investigate, in individuals with obesity, the interplay among EVs derived from cells relevant for the atherosclerotic process (i.e., platelets, endothelium, monocytes/macrophages, and neutrophils), their miRNA content and proprotein convertase subtilisin/kexin type 9 (PCSK9), one of the main regulators of low-density lipoprotein receptor (LDLR).Methods and Results: EVs have been isolated from 936 individuals with obesity (body mass index = 33.6 ± 5.6 Kg/m2) and a raised cardiovascular risk (e.g., LDL-C = 131.6 ± 36.4 mg/dL, HOMA-IR = 3.1, and roughly 50% on anti-hypertensive medications). PCSK9 levels were negatively associated with EV count in the range 150–400 nm and with those derived from macrophages (CD14+), endothelium (CD105+), and neutrophils (CD66+). The association between PCSK9 and platelet-derived EVs (CD61+) was modified by platelet counts. PCSK9 was significantly associated with five EV-derived miRNAs (hsa-miRNA−362−5p,−150,−1244,−520b-3p,−638). Toll-like receptor 4 and estrogen receptor 1 were targeted by all five miRNAs and LDLR by four. The effect on LDLR expression is mainly driven by hsa-miR-150. Considering the implication of EV in atherosclerosis onset and progression, our findings show a potential role of PCSK9 to regulate EV-derived miRNAs, especially those involved in inflammation and expression of low-density lipoprotein receptor (LDLR) receptor.

Objective To assess the circulating micro-RNA-150 (miR-150) expression in patients with chronic myeloid leukemia (CML) in relation to imatinib response. Methods Sixty patients with CML and 20 age- and sex-matched control subjects were enrolled. Circulating miR-150 levels were assessed by quantitative real-time polymerase chain reaction on days 0, 14, and 90 of imatinib therapy for patients and once for control subjects. Results The baseline miR-150 expression was significantly lower in patients with CML than in control subjects with subsequent elevation at 14 and 90 days after the start of imatinib treatment. Early treatment response (ETR) at 90 days was the main study outcome. The miR-150 expression had a significantly higher level in patients with CML with ETR. On multivariate analysis, miR-150 on day 14 was significantly related to ETR in patients with CML with predictive efficacy (area under the curve = 0.838, 72.9% sensitivity, and 84.2% specificity). Conclusion We found that miR-150 expression on day 14 of imatinib treatment is a useful early predictive candidate for imatinib response in patients with CML. [ABSTRACT FROM AUTHOR]

Background. The sequential organ failure assessment (SOFA) score, designed to evaluate sepsis-associated organ dysfunction in intensive care unit (ICU) patients, is associated with the prognosis of sepsis patients. MicroRNA-150 (miR-150) is one of the first miRs to be detected in patients with sepsis and other critical illnesses, and to have an association with the prognosis of critical illness and sepsis. Objectives. To assess the predictive value of the combination of the SOFA score and miR-150 levels for the prognosis of sepsis patients. Materials and methods. We retrospectively included 437 adult patients with sepsis who were divided into a death group (n = 138, 31.6%) and a survival group (n = 299, 68.4%), according to their survival status at the 28-day follow-up. Binary logistic regression was performed to identify independent associations. Receiver operator characteristic (ROC) curve was employed to assess the predictive values. The Z-test was used to compare the area under curve (AUC). Results. Multivariate analysis demonstrated that miR-150 (odds ratio (OR): 0.549, 95% confidence interval (95% CI) [0.372, 0.826], p < 0.001), the SOFA score (OR: 1.216, 95% CI [1.039, 1.807], p = 0.008), age, procalcitonin (PCT), and septic shock were independently associated with 28-day mortality of sepsis patients following the adjustment for chronic renal failure, hypertension, diabetes mellitus, activated partial thromboplastin time (APTT), serum creatinine (SCr), blood urea nitrogen (BUN), and total bilirubin (TBil). The AUC of miR-150, the SOFA score and their combination in predicting the 28-day mortality of sepsis patients was 0.762 (standard error (SE): 0.023, 95% CI [0.717, 0.808]), 0.735 (SE: 0.025, 95% CI [0.687, 0.784]) and 0.886 (SE: 0.015, 95% CI [0.857, 0.916]), respectively. The AUC of their combined prediction was significantly greater than the independent prediction (0.886 compared to 0.762, Z = 4.516, p < 0.001; 0.886 compared to 0.735, Z = 5.179, p < 0.001). The sensitivity and specificity of combination prediction were 86.2% and 80.6%, respectively. Conclusions. The combination of the SOFA score and miR-150 could improve the prediction of prognosis in sepsis patients. [ABSTRACT FROM AUTHOR]

Sodium butyrate (NaB) in the gut of animals possesses the potential to modulate lipid metabolism, regulate innate immunity and protect intestinal health. Accumulating data have supported the important function of metabolites of intestinal microflora (MIM) in non‐alcoholic fatty liver disease (NAFLD). This study intended to investigate the role of NaB in NAFLD and its specific mechanism. Mice were fed a high‐fat diet (HFD) for 16 weeks to establish the NAFLD mouse model. The mice were intragastrically administrated MIM (200 µL/day) or NaB (200 mg/kg/day) by gavage for another 8 weeks. The morphology of liver tissues was observed by hematoxylin and eosin (H&E) staining, and the lipid deposition of liver tissues was examined by oil red O staining. The NAFLD cell model was constructed in alpha mouse liver 12 (AML12) cells by 24 hours of stimulation with 0.5 mM free fatty acids. After treatment with 10 mM NaB, AML12 cells were transfected with mimic‐miR‐150 or inhibitor‐miR‐150. Quantitative real‐time polymerase chain reaction (qRT‐PCR) and western blotting were used to measure the contents of interleukin 1β (IL‐1β), IL‐6 and tumour necrosis factor α (TNF‐α) and the expression of microRNA (miR)‐150 and CXCR4 in liver tissues of mice and in AML12 cells. A luciferase reporter assay was applied to verify the binding relationship between miR‐150 and CXCR4. The H&E and oil red O staining results showed hepatic steatosis in the liver tissues of HFD‐fed mice. There were elevated contents of triacylglycerides (TG), total cholesterol (TC), high‐density lipoprotein cholesterol (HDL‐C), low‐density lipoprotein cholesterol (LDL‐C), fasting blood glucose, enhanced activities of alanine aminotransferase(ALT) and aspartate aminotransferase(AST), increased homeostatic model assessment of insulin resistance scores and increased inflammatory responses in the serum of HFD‐fed mice. However, intervention with MIM or NaB reversed the above trends, indicating that MIM or NaB intervention relieved hepatic steatosis in mice. HFD‐fed mice had downregulated expression of miR‐150, whereas the expression level was upregulated after MIM or NaB treatment. Sodium butyrate attenuated NAFLD progression by regulating miR‐150. MiR‐150 can negatively target CXCR4. Sodium butyrate mitigates HFD‐induced NAFLD in mice by upregulating miR‐150 expression to downregulate CXCR4. [ABSTRACT FROM AUTHOR]

Abstract Background & Aims Anti-mitochondrial-autoantibodies (AMA) remain a hallmark of Primary Biliary Cholangitis (PBC) however approximately 10% of patients test negative for these antibodies. They do not differ in terms of biochemistry or clinical presentation from AMA positive ones. Epigenetics play a key role in immune signalling. Two microRNAs (miRs), namely, miR-21 and miR-150 are known to be involved in liver inflammation and fibrosis. The expression of those two microRNAs and their downstream targets were analyze in the context of AMA-status and the stage of liver fibrosis. Methods The relative levels of miR-21 and miR-150 and their target genes: cMyb, RAS-guanyl-releasing protein-1(RASGRP1), and DNA-methyltransferase-1(DNMT1) were determined by Real-Time PCR in serum, liver tissue and peripheral blood mononuclear cells (PBMCs) of patients with PBC. Results Serum expressions of miR-21 and miR-150 were significantly enhanced in AMA-negative patients, and they inversely correlated with disease-specific AMA titers in PBS patients. In PBMCs, an increased expression of miR-21 correlated with decreased levels of RASGRP1 and DNMT1 mRNAs whereas, the level of miR-150 remained comparable to controls; and cMyb mRNA was downregulated. In cirrhotic livers, the level of miR-21 was unchanged while miR-150 expression was increased. Conclusion This study convincingly report, that AMA-negative PBC is characterized by notable alternations of miR-21 and miR-150 and their downstream targets compared to AMA-positive patients underlining their possible importance in the induction of the disease and its progression to fibrosis.

Abstract Background Noncoding RNAs, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are becoming key parts in the development of multidrug resistance (MDR) in T-cell acute lymphoblastic leukemia (T-ALL). Abnormal expression in sialyated N-glycans have been observed in MDR leukemia. However, the role of sialylation regulated MDR remains poorly understood. The aim of this work is to analyze the alternation of N-glycans in T-ALL MDR. Methods Here, mass spectrometry (MS) is analyzed to screen the N-glycan profiles from ALL cell line CR and adriamycin (ADR)-resistant CR (CR/A) cells. The expression of sialyltransferase (ST) genes in T-ALL cell lines and bone marrow mononuclear cells (BMMCs) of T-ALL patients were analyzed using qRT-PCR. Functionally, T-ALL cell proliferation and MDR are detected through CCK8 assay, colony formation assay, western blot and flow cytometry. RIP assay and Dual-luciferase reporter gene assay confirm the binding association between ZFAS1 and miR-150. Xenograft nude mice models are used to determine the role of ST6GAL1 in vivo. Results Elevated expression of α2, 6-sialyltransferase 1 (ST6GAL1) has been detected. The altered level of ST6GAL1 was corresponding to the drug-resistant phenotype of T-ALL cell lines both in vitro and in vivo. ZFAS1/miR-150/ST6GAL1 axis was existed in T-ALL cell lines. MiR-150 was downregulated and inversely correlated to ST6GAL1 expression. ZFAS1 was a direct target of miR-150 and positively modulated ST6GAL1 level by binding miR-150. ZFAS1/miR-150/ST6GAL1 axis functioned to regulate ADR-resistant cell growth and apoptosis. Besides, EGFR was demonstrated to be a substrate of ST6GAL1, and the sialylated EGFR had an impact on the PI3K/Akt pathway. Conclusion Results suggested that ZFAS1/miR-150/ST6GAL1 axis involves in the progression of T-ALL/MDR further mediates sialylated EGFR via PI3K/Akt pathway. This work might have an application against T-ALL MDR.

Purpose: Altered miRNAs play a crucial role in the emergence of the breast cancer stem cell (BCSC) phenotype. The interplay between miRNAs and methylation enzymes has been documented. One of the most aggressive breast cancer cell lines, MDA-MB-231, has expressed much more DNMT3B than DNMT3A. This study aims to evaluate the ability of miR-203 restoration and miR-150 inhibition to regulate DNMT3B and DNMT3A to modify the methylation level of BCSC-associated genes. Methods: MDA-MB-231 cells were transfected with miR-203 mimic or miR-150 inhibitor or DNMT3B siRNA, and downstream analysis was performed by flow cytometry, real-time PCR and Western blotting. Results: DNMT3A and DNMT3B are regulated both by miR-203a-3p and miR-150-5p. Transfection with miR-203 mimic and miR-150 inhibitor significantly reduced the CD44+CD24− subpopulation and down-regulated the expression of CD44 mRNA by increasing promoter methylation levels. SiRNA knockdown of DNMT3B increased the CD44+CD24− subpopulation and the expression of CD44 and ALDH1A3 by decreasing methylation density. The inhibition of miR-150 down-regulated OCT3/4 and SOX2 expression without affecting methylation levels, while miR-203 restoration and miR-150 inhibition down-regulated NANOG expression by elevating the methylation level. A positive-feedback loop was found between miR-203 and its target DNMT3B, as restoring miR-203 suppressed DNMT3B, while knocking down DNMT3B up-regulated miR-203. The restoration of miR-203 and knockdown of DNMT3B decreased methylation levels and increased the expression of miR-141 and miR-200c. Conclusions: The study concluded that miR-203 and miR-150 play a role in the regulation of genes involved in BCSC methylation, including other miRNAs, by targeting DNMT3B and DNMT3A. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Oral squamous cell carcinoma (OSCC) accounts for 90% of head and neck cancers, and its 5-year overall survival is very poor. MiR-150 is usually downregulated and acts as tumor suppressor in multiple cancers. The aim of our study is to explore the functions of miR-150 in OSCC. PATIENTS AND METHODS: Expressions of miR-150 and HMGA2 mRNA in OSCC tissues and cells were analyzed by qRT-PCR. Methyl Thiazolyl Tetrazolium (MTT) and transwell assays were conducted to assess the cell viability and invasive abilities. Western blot was conducted to assess the protein levels of epithelial-mesenchymal transition (EMT) markers. Luciferase reporter assay was carried out to verify miR-150 directly binding to HMGA2 in SCC25 cells. RESULTS: MiR-150 was low expressed and HMGA2 was highly expressed in OSCC tissues and cells. Downregulation of miR-150 or upregulation of HMGA2 predicted poor prognosis of OSCC patients. MiR-150 overexpression inhibited the abilities of viability, invasive and the EMT by targeting HMGA2 in OSCC cells. HMGA2 was a target gene of miR-150 and its expression was regulated by altering the expression of miR-150 in OSCC cells. HMGA2 reversed partial roles of miR-150 on cell viability and invasion in OSCC. CONCLUSIONS: MiR-150 impaired cell viability, invasion and EMT via binding to HMGA2 of OSCC. Our research demonstrates that miR-150 plays a critical role in the progression of OSCC. miR-150 might be a candidate molecular marker and a novel therapy target for OSCC patients. [ABSTRACT FROM AUTHOR]

miR-150 was found to target the 3′-untranslated regions of AKT3, and the AKT pathway was affected by SR protein kinase 1 (SRPK1). However, the expression and significance of miR-150, AKT3 and SRPK1 in acute lung injury (ALI) were not clear. Here, we found that the expression of miR-150 was significantly reduced, while the expression of AKT3 and SRPK1 were markedly increased in LPS-treated A549, THP-1 and RAW 264.7 cells. miR-150 significantly decreased levels of pro-inflammatory cytokines IL-1β, IL-6 and TNF-α, reduced the expression of AKT3, but had no impact on SRPK1 expression compared with the control group in LPS-treated A549, THP-1 and RAW 264.7 cells. AKT3 silencing only reduced the production of pro-inflammatory cytokines and showed no effect on miR-150 and SRPK1 expression. Finally, we observed that miR-150 mimics and/or silencing of SRPK1 decreased the expression of AKT3 mRNA. Besides, over-expression of miR-150 or silencing of SRPK1 also reduced the expression of AKT3 protein, which exhibited the lowest level in the miR-150 mimics plus si-SRPK1 group. However, si-SRPK1 had no effect on miR-150 level. In conclusion, miR-150 and SRPK1 separately and cooperatively participate into inflammatory responses in ALI through regulating AKT3 pathway. Increased miR-150 and silenced SRPK1 may be a novel potential factor for preventing and treating more inflammatory lung diseases. [ABSTRACT FROM AUTHOR]

Background/Aims: To investigate the biological roles and underlying molecular mechanisms of long non-coding RNA (lncRNA) PVT1 in Hepatocellular carcinoma (HCC). Methods: qRT-PCR was performed to measure the expression of miRNA and mRNA. Western blot was performed to measure the protein expression. CCK-8 assay was performed to determine cell proliferation. Flow cytometry was performed to detect cell apoptosis. Wounding-healing assay and Transwell assay was performed to detect cell migration and invasion. Dual luciferase reporter assay was performed to verify the target relationship. Quantichrom iron assay was performed to check uptake level of cellular iron. Results: PVT1 expression was up-regulated in HCC tissues and cell lines. Function studies revealed that PVT1 knockdown significantly suppressed cell proliferation, migration and invasion, and induced cell apoptosis in vitro. Furthermore, PVT1 could directly bind to microRNA (miR)-150 and down-regulate miR-150 expression. Hypoxia-inducible protein 2 (HIG2) was found to be one target gene of miR-150, and PVT1 knockdown could inhibit the expression of HIG2 through up-regulating miR-150 expression. In addition, the expression of miR-150 was down-regulated, while the expression of HIG2 was up-regulated in HCC tissues and cell lines. Moreover, inhibition of miR-150 could partly reverse the biological effects of PVT1 knockdown on proliferation, motility, apoptosis and iron metabolism in vitro, which might be associated with dysregulation of HIG2. In vivo results showed that PVT1 knockdown suppressed tumorigenesis and iron metabolism disorder by regulating the expression of miR-150 and HIG2. Conclusion: Taken together, the present study demonstrates that PVT1/miR-150/HIG2 axis may lead to a better understanding of HCC pathogenesis and provide potential therapeutic targets for HCC.

Background/Aims: Interleukin-1 (IL-1) is known to be involved in cartilage degeneration following joint injury or due to osteoarthritis. In the present study, we explored the effects of miR-150 on IL-1-stimulated human chondrogenic cells ATDC5. Methods: ATDC5 cells were transfected with the mimic, inhibitor or negative controls specific for miR-150, and subsequently treated by IL-1. CCK8 assay, PI and FITC-conjugated Annexin V double-staining, Western blot, qRT-PCR and ELISA assay were performed to determine the changes of cell viability, apoptosis, and the release of pro-inflammatory cytokines. Targeting relationship between miR-150 and KLF2 was detected by dual luciferase activity assay. Results: IL-1 reduced cell viability, induced apoptosis, and enhanced the expression and release of pro-inflammatory cytokines (IL-6, IL-8 and TNF-α) in ATDC5 cells. IL-1 also increased the expression of miR-150. Suppression of miR-150 alleviated IL-1-induced cell damage in ATDC5 cells, while overexpression of miR-150 resulted in an opposite impact. KLF2 was negatively regulated by miR-150, and it was proved as a target gene of miR-150. KLF2 overexpression exhibited protective actions in IL-1-injured ATDC5 cells, even if miR-150 was suppressed in cell. Moreover, IL-1-induced activation of NF-kB and Notch pathways was alleviated by KLF2 overexpression. Conclusions: Suppression of miR-150 led to up-regulation of KLF2, which in turn protected ATDC5 cells against IL-1-induced injury.

Circular RNAs (circRNAs) participate in the pathogenesis of various diseases by sponging microRNAs (miRs). However, the roles of circRNAs remain unreported in glomerular diseases. We previously reported that miR-150 positively correlated with renal chronicity index in patients with lupus nephritis (LN). We aimed to investigate renal circRNA profiling and the interaction between circRNAs and miR-150 in LN patients. Six renal biopsies from untreated female patients with LN class IV and five normal kidney tissues from urology patients were used for circRNA sequencing. 171 circRNAs with 2-fold differential expression were identified in LN compared with normal control. Ten selected circRNAs were validated by real-time qPCR, and seven circRNAs showed the same significant increases as the sequencing results. circHLA-C positively correlated with proteinuria (R = 0.92, p

OBJECTIVE: The aim of this study was to explore the influences of micro ribonucleic acid (miR)-150 on the proliferation and apoptosis of mantle-cell lymphoma (MCL) cells and to investigate the potential underlying mechanism. PATIENTS AND METHODS: Differentially expressed miRNAs in MCL tissues were excavated via microarray analysis of miRNA expression profiles. Subsequently, the expression of miRNAs were verified by quantitative Reverse Transcription-Polymerase Chain Reaction (RT-qP-CR). The influence of miRNA expression on the survival of patients was detected based on clinical data. Besides, the potential targets of miRNAs were determined using Luciferase reporter gene assay combined with qRT-PCR and Western blotting. Primary tumor cells were extracted, and the influences of miR-150 expression on cell proliferation were detected via Cell Counting Kit (CCK)-8 assay and 5-ethynyl-2'-deoxyuridine (EdU) staining assay. Finally, Western blotting and flow cytometry were performed to explore the impact of miR-150 on the apoptosis of primary tumor cells. RESULTS: Microarray analysis of miRNA expression profiles and RT-qPCR verified that the expression levels of hsa-miR-486, hsa-miR-4746, and hsa-miR-3158 rose considerably in MCL tissues, while those of hsa-miR-29b-3p, hsa-miR-150, and hsa-miR-142-5p remarkably declined. According to the results of survival analysis, the survival time was notably prolonged in patients with higher expression levels of miR-150 and miR-486, especially in those with higher expression level of miR-150. Luciferase reporter gene assay and RT-qPCR and Western blotting results demonstrated that miR-150 negatively regulated the expression level of MET. Subsequent CCK-8 assay and EdU staining results revealed that up-regulation of miR-150 significantly suppressed the proliferation of primary MCL cells. Finally, Western blotting and flow cytometry found that increased expression of MET remarkably facilitated the apoptosis of primary MCL cells. CONCLUSIONS: MiR-150 inhibits the proliferation and promotes the apoptosis of MCL cells by negatively regulating MET expression. [ABSTRACT FROM AUTHOR]

BACKGROUND: Long non-coding RNA (lncNRA) forkhead box D3 antisense RNA 1 (FOXD3-AS1) has been proved to promote or suppress the occurrence and development of multiple types of human tumors. However, the function and mechanism of FOXD3-AS1 in non-small cell lung cancer (NSCLC) are scarcely understood. METHODS: qRT-PCR was used for detecting FOXD3-AS1, miR-150 and SRC kinase signaling inhibitor 1 (SRCIN1) mRNA expression in NSCLC tissues, and the relationship between pathological characteristics of NSCLC patients and FOXD3-AS1 expression level was analyzed. With human NSCLC cell lines H1299 and A549 as cell models, CCK-8 and BrdU assays were employed for detecting cancer cell proliferation, and Transwell assay was employed for detecting cell invasion ability. Dual luciferase reporter gene assay and RNA immunoprecipitation (RIP) assay were used for the verification of the targeting relationshipe between FOXD3-AS1 and miR-150, and Western blot was employed for detecting SRCIN1 protein expression. RESULTS: FOXD3-AS1 expression was significantly reduced in NSCLC tissues and cell lines, and low expression of FOXD3-AS1 was closely related to positive lymph node metastasis and relatively high tumor grade. FOXD3-AS1 over-expression inhibited the proliferation and invasion of H1299 cell lines, while its knockdown promoted the proliferation and invasion of A549 cells. Additionally, it was confirmed that FOXD3-AS1 suppressed the expression of miR-150 by targeting it, and up-regulated the expression of SRCIN1. CONCLUSIONS: FOXD3-AS1 indirectly enhances the expression of SRCIN1 by targeting miR-150, thereby inhibiting NSCLC progression. [ABSTRACT FROM AUTHOR]

In the present study, we aimed to illustrate the roles and working mechanisms of long non-coding RNA (lncRNA) rhabdomyosarcoma 2-associated transcript (Rmst) and EGb761 in oxygen–glucose deprivation (OGD)-induced brain microvascular endothelial cells (BMECs). OGD exposure augmented the level of Rmst while reduced the expression of miR-150 in bEnd.3 cells. MiR-150 could directly bind to Rmst in bEnd.3 cells. Rmst silencing abrogated the inhibitory influences on the proliferation and migration and the promoting impact on the apoptosis of bEnd.3 cells caused by OGD exposure. Rmst overexpression intensified OGD-induced injury in bEnd.3 cells. OGD induced the injury of bEnd.3 cells through Rmst/miR-150 axis. EGb761 attenuated the damage in bEnd.3 cells induced by OGD through targeting Rmst/miR-150 axis. EGb761 might be an effective therapeutic agent to protect brain microvascular endothelial cells from hypoxia–ischemia induced injury. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia (AML) is a highly aggressive disease that causes high mortality. Long noncoding RNA (lncRNA) have studied in recent years that could be a potential biomarker and therapeutic target. Therefore, it is urgently necessary to explore the novel lncRNAs in AML. Microarray analysis was performed to determine the differentially expressed lncRNAs between mononuclear cells of AML and normal samples. The biological function of lncRNA on cell proliferation and migration was measured in vitro. The predicted downstream target of lncRNA was validated by dual‐luciferase reporter assay, RNA immunoprecipitation, RNA pull‐down, and rescue experiments. The tumor formation and metastasis study were conducted in vivo. The expression of lncRNA in clinical samples was determined by a quantitative reverse transcription‐polymerase chain reaction. LINC00449 was one of the most differentially expressed lncRNA which is mainly located in the cytoplasm. We found that overexpression of LINC00449 could inhibit the cell proliferation and invasion of AML cells in vitro and in vivo. Besides, miR‐150 was identified as the downstream target gene that was negatively regulated by LINC00449 and FOXD3 was targeted by miR‐150. The results were confirmed by dual‐luciferase reporter assay, RNA immunoprecipitation, RNA pull‐down, rescue experiments, and in vivo assays. Patients with AML with high expression of LINC0049 may characterize a favorable survival. All the above‐mentioned findings indicated that the LINC00449/miR‐150/FOXD3 signaling pathway might represent a novel prognostic biomarker or therapeutic target for the treatment of AML. [ABSTRACT FROM AUTHOR]

Background: Deep venous thrombosis (DVT) constitutes a major global disease burden. Endothelial progenitor cells (EPCs) have been described in association with recanalization of venous thrombus. Furthermore, emerging evidence suggests microRNAs are involved in this progression. The goal of this study was to investigate the influence of miR-150 on the behavior of EPCs and its potential contribution in venous thrombosis resolution. Methods: We isolated and cultured EPCs from healthy adults. Next, early EPCs or endothelial colony-forming cells (ECFCs or late EPCs) were transfected with miR-150 agomir and antagomir. Gene expression profiles, proliferation, cytokine secretion, and angiogenic capacity of early EPCs and ECFCs were examined. The effects of miR-150 on c-Myb expression and Akt/FOXO1 signaling were also evaluated. Furthermore, a rat model of venous thrombosis was constructed to determine the in vivo function of EPCs. Results: Our results showed that miR-150 overexpression in early EPCs significantly promoted differentiation to ECFCs and contributed to proliferation and tube formation. However, suppression of miR-150 in late EPCs inhibited proliferation and tube formation. Moreover, we identified that this progression is regulated by inhibition of c-Myb and activation of the Akt/FOXO1 pathway. Our findings also showed that miR-150 led to the enhanced resolution ability of EPCs in a rat venous thrombosis model. Conclusions: In this study, we present a novel mechanism of miRNA-mediated regulation of EPCs and Akt activation in thrombus resolution. [ABSTRACT FROM AUTHOR]

Melanoma is a common skin cancer and it can lead to high mortality probably by early invasion and metastasis. LncRNA MIAT is involved in tumor proliferation, invasion and epithelial-to-mesenchymal transition (EMT). However, the roles of MIAT in melanoma still require further investigation. Thus, the aim of the study is to investigate the roles of MIAT in melanoma, especially the effects of MIAT on EMT of melanoma cancer cells. The results showed that the expression of MIAT was significantly upregulated in melanoma tissue and cells compared with the normal skin and normal melanocytes; moreover, miR-150 was confirmed as a target of MIAT. Furthermore, knockdown of MIAT inhibited cell proliferation and invasion in melanoma cancer cells and transfection of miR-150 inhibitors partial abrogated the anti-tumor effects of MIAT siRNA. In addition, MIAT siRNA also inhibited the EMT of melanoma cells, while miR-150 inhibitors can reverse the effects of MIAT siRNA. Finally, knockdown of MIAT also inhibited the carcinogenic effects of melanoma in vivo by targeting miR-150. In conclusion, we reported that MIAT promotes the proliferation, invasion and EMT of melanoma cells via targeting miR-150, which suggested that MIAT might be a therapeutic target for the treatment of melanoma. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) are promising therapeutic cells for preventing apoptosis and abrogating cellular injury. Apoptosis of macrophages and the resulting dysfunction play a critical pathogenic role in acute respiratory distress syndrome (ARDS). Herein, the anti-apoptosis effects of bone marrow MSCs (BMSCs) on RAW264.7 were investigated by transwell assay. Compared to lipopolysaccharide (LPS) stimulation, the treatment of BMSCs decreased the level of cleaved caspase-3 protein, the ratio of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells, the level of caspase3-positive cells, and the accumulation of reactive oxygen species (ROS). Moreover, the expression of Bcl-2 and the level of mitochondrial membrane potential (MMP) were increased. Also, it was found that miR-150 disruption of BMSCs remarkably improved the efficiency of the treatment with LPS-stimulated RAW264.7 cells. The study demonstrated that the suppression of miR-150 facilitated the translation of MTCH2 gene and MTCH2-regulated mitochondria transfer from BMSCs to RAW264.7 cells, suggested that miR-150-mediated BMSCs has therapeutic potential for ARDS. • MiR-150 regulated the therapeutic effect of BMSCs in LPS-induced RAW264.7 apoptosis. • MTCH2 is the direct target gene of miR-150. • MTCH2 regulates the mitochondria transfer from BMSC to LPS-induced RAW264.7 to ameliorate the apoptosis of RAW264.7. [ABSTRACT FROM AUTHOR]

A number of studies suggest an association between miRNAs and diffuse large B-cell lymphoma (DLBCL). The present study aimed to investigate the prognostic value of microRNA (miR-150) in primary gastrointestinal (PGI)-DLBCL, by assessing the association between miR-150 expression and clinicopathological characteristics in patients with PGI-DLBCL. A total of 84 patients diagnosed with PGI-DLBCL were recruited and both tumor and adjacent non-tumor tissue samples were collected. miR-150 expression was assessed via reverse transcription-quantitative (RT-q)PCR analysis. The results demonstrated that miR-150 expression was significantly lower in PGI-DLBCL tissues compared with adjacent non-tumor tissues. Furthermore, receiver operating characteristic (ROC) curve analysis indicated that the optimal cut-off value of miR-150 for predicting survival was 8.965 with high sensitivity (79.8%) and specificity (77.1%). Patients were divided into two groups according to this cut-off value, as follows: High (n=18) and low expression (n=66) groups. Low miR-150 expression was significantly associated with clinical stage, International Prognostic Index (IPI), Eastern Cooperative Oncology Group status and use of rituximab. RT-qPCR analysis demonstrated that miR-150 expression was significantly lower in patients with high IPI scores compared with patients with low IPI scores. Downregulated miR-150 expression was significantly associated with shorter overall survival (OS) time and progression-free survival (PFS) time in patients with PGI-DLBCL. Furthermore, miR-150 level and IPI score were identified as two risk factors for OS and PFS. The diagnostic value of miR-150 was evaluated via ROC curve analysis, with an area under the curve value of 0.882. Taken together, the results of the present study suggest that miR-150 is a potential diagnostic marker of PGI-DLBCL, and may also serve as a useful prognostic factor for survival outcomes in patients with PGI-DLBCL. [ABSTRACT FROM AUTHOR]

The dental pulp can be affected by thermal, physical, chemical, and bacterial phenomena that stimulate the inflammatory response. The pulp tissue produces an immunological, cellular, and vascular reaction in an attempt to defend itself and resolve the affected tissue. The expression of different microRNAs during pulp inflammation has been previously documented. MicroRNAs (miRNAs) are endogenous small molecules involved in the transcription of genes that regulate the immune system and the inflammatory response. They are present in cellular and physiological functions, as well as in the pathogenesis of human diseases, becoming potential biomarkers for diagnosis, prognosis, monitoring, and safety. Previous studies have evidenced the different roles played by miRNAs in proinflammatory, anti-inflammatory, and immunological phenomena in the dental pulp, highlighting specific key functions of pulp pathology. This systematized review aims to provide an understanding of the role of the different microRNAs detected in the pulp and their effects on the expression of the different target genes that are involved during pulp inflammation.