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Asthma is a respiratory disease with a clinically high incidence, and repeated attacks of asthma severely affect the quality of life and even pose a threat to health, leading to severe burdens on families and even the society. A thorough understanding of the pathogenesis of asthma is essential for the prevention and treatment of asthma. This study aimed to examine the effect of the microRNA miR-27a on asthma and its relationship with mitogen activated protein kinase 4 (MAP2K4). Patients with asthma admitted to our hospital from August 2016 to August 2018 and healthy participants in the same period were included in this prospective analysis. The mRNA expression levels of miR-27a and MAP2K4 in peripheral blood were determined. Airway smooth muscle cells (ASMCs) were used to study the effects of miR-27a and MAP2K4 on cell biological behavior. The relationship between miR-27a and MAP2K4 was verified using dual-luciferase reporter assay. miR-27a expression was increased and MAP2K4 mRNA expression was decreased in asthma (P < 0.05). Increasing miR-27a expression and inhibiting MAP2K4 expression could enhance the activity of ASMCs, whereas inhibiting miR-27a expression and increasing MAP2K4 expression had the opposite effect (P < 0.05). Dual-luciferase reporter assay results showed that the fluorescence activity of MAP2K4-wild type was inhibited by increased miR-27a expression (P < 0.05). miR-27a promotes the proliferation and invasion of ASMCs by targeting MAP2K4 and is involved in the occurrence of asthma.

Ovarian hyperstimulation syndrome (OHSS) is one of the most dangerous iatrogenic complications in controlled ovarian hyperstimulation (COH). The exact molecular mechanism that induces OHSS remains unclear. In recent years, accumulating evidence found that exosomal miRNAs participate in many diseases of reproductive system. However, the specific role of miRNAs, particularly the follicular fluid‐derived exosomal miRNAs in OHSS remains controversial. To identify differentially expressed follicular fluid exosomal miRNAs from OHSS and non‐OHSS patients, the analysis based on miRNA‐sequence was conducted. The levels of 291 miRNAs were significantly differed in exosomes from OHSS patients compared with normal control, and exosomal miR‐27 was one of the most significantly down‐regulated miRNAs in the OHSS group. By using MiR‐27 mimic, we found it could increase ROS stress and apoptosis by down‐regulating the expression of p‐ERK/Nrf2 pathway by negatively regulating SPRY2. These data demonstrate that exosomal miRNAs are differentially expressed in follicular fluid between patients with and without OHSS, and follicular fluid exosomal miR‐27 may involve in the pathological process of OHSS development.

Objective: to evaluate the expression levels of miRNA (miR-27, miR-101, miR-142, miR-339 and miR-424) and its relationship with clinical and laboratory parameters in lung transplant recipients. Materials and methods. The study included 57 lung recipients aged 10 to 74 years (35 ± 15), including six children (9%) – four boys 10, 12, 13 and 17 years and girls 13 and 14 years old – and 51 adult recipients, including 30 men (62.5%). The control group was made up of 14 healthy individuals that were not significantly different by gender and age. Expression levels of the microRNAs studied in blood plasma were determined via quantitative polymerase chain reaction (PCR). Correlations of miRNA expression levels with complete blood count and biochemical blood test indicators were analyzed. Results. Patients with end-stage chronic respiratory failure (potential lung recipients) were found to have significantly higher expression levels of miR-27, miR-101 and miR-339 in plasma than the healthy individuals (p = 0.02, p = 0.03 and p = 0.01, respectively). The expression level of miR-339 correlated with the age of potential lung recipients (p = 0.04). It was a negative correlation (r = –0.46). The expression levels of the other four miRNAs were age independent. The average expression level of miR-424 in lung recipients in the long-term period after lung transplant was higher than in waitlisted patients (p = 0.03). Analysis of the relationship between miRNA expression levels and external respiration function in the long-term post-transplant period showed that miR-142 expression level (r = 0.61; p = 0.04) positively correlates with the Tiffeneau-Pinelli index. This strong correlation, which exceeds 85%, indicates the presence of restrictive lung diseases. A year and more after transplantation, it was found that in the recipients, there were close positive correlations between miR-27, miR-142, miR-424 expression levels and blood leukocyte concentration, as well as between the miR-142 expression level and the sCD40L concentration during this period. Conclusion. A comparative study of the expression level of miRNAs (miR-27, miR-101, miR-142, miR-339 and miR-424) in the blood plasma of patients suffering from end-stage chronic lung diseases of various origin and in lung recipients enables us to conclude that further studies of the miRNA panels are needed in order to assess their effectiveness as potential molecular and genetic markers of post-transplant complications.

Diabetic wounds increase morbidity and decrease quality of life in patients with type 2 diabetes. Serum miR-27-3p levels are reportedly elevated in type 2 diabetic patients. In the present study, we explored the role of miR-27-3p during wound healing. We found that miR-27-3p is overexpressed in cutaneous fibroblasts of diabetic patients and mice. miR-27-3p knockdown enhanced the proliferation and migration of fibroblasts, while suppressing the incidence of fibroblast apoptosis. Overexpressing miR-27-3p in fibroblasts had the opposite effects. We also identified neuro-oncological ventral antigen 1 (NOVA1) as a target of miR-27-3p in fibroblasts. Knocking down NOVA1 using targeted siRNA mimicked the effects of miR-27-3p overexpression in fibroblasts. Administration of miR-27-3p to the area around wounds inflicted in mice delayed healing of those wounds. This suggests that miR-27-3p suppresses fibroblast function by targeting NOVA1, which results in the slowing of wound healing. These findings may offer a new approach to the treatment of diabetic wound healing.

Purpose: We investigated the pathogenesis of idiopathic nephrotic syndrome (INS) by measuring the effects two specific miRNAs on Th2 cells in children with this disease.Methods: After informed consent, we enrolled 20 children with active INS before steroid initiation, 20 children with INS in remission after steroid therapy, and 20 age-matched healthy controls. Flow cytometry was used to measure the levels of Th2 cells and a cytometric bead array was used to measure the levels of IgE, interleukin (IL)−4, and IL-13. RT-PCR was used to measure the levels of miR-24 and miR-27 in CD4+TCD25− cells. PBMCs were isolated using Ficoll density gradient centrifugation, and transfected with different mimic or inhibitor miRNAs. RT-PCR was used to measure the expression of different RNAs, and flow cytometry was used to determine the percentage of Th2 cells.Results: Relative to healthy controls, children with active INS had higher percentages of Th2 cells (P < 0.05), but there was no significant difference in controls and children in remission. The plasma levels of IgE, IL-4, and IL-13 were significantly increased in children with active INS (P < 0.05). There were lower levels of miR-24 and miR-27 in children with active non-atopic INS (P < 0.05). Transfection experiments indicated that upregulation of each miRNA decreased the percentage of Th2 cells and the level of IL-4 (P < 0.05), and down-regulation of each miRNA had the opposite effects (P < 0.05).Conclusion: Children with active INS, with or without atopy, had higher levels of IgE, possibly related to their higher levels of IL-13 and IL-4 due to a drift toward Th2 cells. miR-24 and miR-27 suppressed the expression of Th2 cells and have a critical function regulating Th2 cell expression in INS.

Objective This study aims to systematically review the role of differentially expressed microRNA (miRNA) in saliva as potential biomarkers in oral cancer patients. Design PubMed, Scopus and EBSCO online data bases were used as well as manual searching to extract studies from January 2008 up to October 2020. Results A total of 14 studies that met the eligibility criteria were included. All selected studies were of case-control type. A total of 25 differentially expressed miRNAs were identified. Thirteen of these miRNAs (Let-7a, miR 27, miR 34, miR 92, miR 124, miR 125a, miR 136, miR139 miR 145, miR 146a, miR 200a, miR 205 and miR 375) were downregulated and other twelve (miR 9, miR 21, miR 31, miR 122, miR 134, miR 184, miR 191, miR 196a, miR 196b, miR 412, miR 512 and miR 8392) were upregulated. Four miRNAs were evaluated in more than one study (miR21, miR31, miR125 and miR 200). Conclusion According to these results, salivary miRNA can aid in diagnosis and prognosis of oral squamous cell carcinoma (OSCC). However, controlled clinical trials with a large sample size are required to validate the differentially expressed miRNAs of the present review.

Long noncoding RNAs (lncRNAs) have emerged as regulators of gene expression and play critical regulatory roles in diverse biological functions and diseases, including cancer. In this study, we report the downregulation of LINC01089 in non-small cell lung cancer (NSCLC) samples, relative to adjacent non-tumor tissues, and demonstrate its role in the inhibition of proliferation, migration, and epithelial-mesenchymal transition (EMT) of NSCLC cells. Mechanistic analysis indicates that LINC01089 acts as a sponge for miR-27a, regulating its expression in NSCLC. Interestingly, LINC01089 mediated the upregulation of SFRP1 expression by inhibiting the Wnt/β-catenin-EMT pathway and inhibiting the epithelial-mesenchymal transition of NSCLC via sponging miR-27a. Overall, our findings highlight LINC01089's tumorigenic role and regulatory mechanism in NSCLC, thereby suggesting its potential as a therapeutic target for managing NSCLC.

IntroductionThis study was undertaken to examine the anticancer effects of the natural product rhein on human leukaemia cells.Material and methodsCell viability was determined by MTT assay. Immunofluorescence staining, DAPI, AO/EB, and annexin V/PI staining were used for the detection of apoptosis. qRT-PCR analysis was used to examine protein expression. Western blot analysis was used to determine protein expression.ResultsThe results revealed that rhein caused a significant (p < 0.05) and dose-dependent decrease in the viability of AML-193 leukaemia cells. It was also revealed that rhein caused morphological changes such as cell rounding in rhein-treated AML-193 cells. The DAPI and AO/EB staining showed that rhein caused remarkable changes in the nuclear morphology of the AML-193 cells, characteristic of apoptosis. The percentage of apoptosis was found to be 3.12%, 14.80%, 30.31%, and 60.85% at the concentrations of 0, 3.5, 7, and 14 µM of rhein, respectively. The expression of Bax, cleaved caspase-3, 9, and cleaved PARP increased concentration dependently, while the expression of Bcl-2 decreased. The effects of rhein were also examined on 11 different miRs, and it was found that rhein specifically and significantly (p < 0.05) inhibited the expression of miR-27. Additionally, inhibition of miR-27 resulted in the decrease of AML-193 viability and upregulation of Cullin 5 (CUL5).ConclusionsTaken together, rhein triggers apoptosis in leukaemia cells and modulates the miR-27/CUL5 axis. As such, rhein may prove to be beneficial in the treatment of leukaemia.

Multiple myeloma (MM) is a malignant tumor disease that seriously affects the health of patients. Previous studies have shown the crucial role of autophagy in the development of MM. Therefore, the study aimed to study the effect of miR-27 on autophagy in MM via NEDD4/Notch1 axis. RT-qPCR or western blot analysis was used to detect the expression of miR-27, NEDD4, and Notch1 in bone marrow tissues and CD138+ plasma cells of patients and MM cells. After gain- and loss-of-function assays in MM cells, proliferation and invasion were assessed by clone formation and Transwell assays. Meanwhile, expression of autophagy-related proteins was measured by western blot analysis, followed by evaluation of autophagosomes and autophagic flow. The targeting relationship was evaluated by luciferase reporter assay, whereas the binding of NEDD4 to Notch1 protein was analyzed by co-immunoprecipitation. The ubiquitination level of Notch1 protein was detected. A nude mouse tumor model was established to determine the role of miR-27 in MM in vivo. miR-27 and Notch1 upregulation and NEDD4 downregulation were observed in bone marrow tissues and CD138+ plasma cells of patients and MM cells. miR-27 negatively targeted NEDD4, while NEDD4 could specifically bind to Notch1 protein to increase Notch1 ubiquitin degradation in MM cells. miR-27 or Notch1 overexpression or NEDD4 silencing diminished autophagy but enhanced proliferation and invasion of MM cells. miR-27 upregulation promoted the formation of subcutaneous tumor in nude mice. Collectively, miR-27 elevated Notch1 expression by targeting NEDD4 and promoted the development of MM by inhibiting cell autophagy, which provides a new idea and basis for MM treatment.

Background: Polymorphism in miR-27a rs895819 has been associated with breast cancer (BC) risk, but studies have reported inconsistent results. This meta-analysis investigated the possible association between miR-27a rs895819 polymorphism and BC risk. Methods: PubMed, EMBASE, Google Scholar, and the Chinese National Knowledge Infrastructure (CNKI) databases were systematically searched to identify relevant studies in English and Chinese. Meta-analyses were performed to examine the association between miR-27a rs895819 and BC susceptibility. Results: A total of 16 case–control studies involving 6118 cases and 7042 controls were included. Analysis using five genetic models suggested no significant association between miR-27a rs895819 polymorphism and BC risk in the total population, or specifically in Asian or Chinese subpopulations. In the Caucasian subpopulation, however, the G-allele and AG genotype at rs895819 were significantly associated with decreased BC risk according to the allelic model (OR 0.90, 95% CI 0.84–0.97, P = .004) and heterozygous model (OR 0.89, 95% CI 0.81–089, P = .02), while the wild-type AA genotype was significantly associated with increased BC risk according to the dominant model (OR 1.13, 95% CI 1.03–1.24, P = .007). Conclusion: These results indicate that among Caucasians, the wild-type AA genotype at rs895819 may confer increased susceptibility to BC, while the G-allele and AG genotype may be protective factors. These conclusions should be verified in large, well-designed studies.

The epithelial sodium channel (ENaC) is expressed in the epithelial cells of the distal convoluted tubules, connecting tubules and cortical collecting duct (CCD) in the kidney nephron. Under the regulation of the steroid hormone aldosterone, ENaC is a major determinant of sodium (Na(+) ) and water balance. The ability of aldosterone to regulate microRNAs (miRs) in the kidney has recently been realized, but the role of miRs in Na(+) regulation has not been well established. Here we demonstrate that expression of a miR cluster mmu-miR-23∼24∼27, is upregulated in the CCD by aldosterone stimulation both in vitro and in vivo. Increasing the expression of these miRs increased Na(+) transport in the absence of aldosterone stimulation. Potential miR targets were evaluated and miR-27a/b was verified to bind to the 3'-untranslated region of intersectin-2, a multi-domain protein expressed in the distal kidney nephron and involved in the regulation of membrane trafficking. Expression of Itsn2 mRNA and protein was decreased after aldosterone stimulation. Depletion of Itsn2 expression, mimicking aldosterone regulation, increased ENaC-mediated Na(+) transport, while Itsn2 overexpression reduced ENaC's function. These findings reinforce a role for miRs in aldosterone regulation of Na(+) transport, and implicate miR-27 in aldosterone's action via a novel target. This article is protected by copyright. All rights reserved.

Background/Aims: Osteoarthritis (OA) is a degenerative joint disease characterized by articular cartilage degradation. The degradation of the extracellular matrix (ECM) of chondrocyte is closely associated with the destruction of joints in OA patients. lncRNAs are non-coding segments of RNA that possess important regulatory functions at the cellular level and in a variety of pathophysiological processes. The present study was conducted to investigate whether lncRNA-CIR regulated the expression of MMP13 as a sponge of miR-27 in OA. Methods: Primary cultured chondrocytes were challenged by IL-1β and TNF-α to simulate OA conditions. qRT-PCR was performed to detect the miR-27, lncRNA-CIR, MMP13 mRNA expression levels. Western blot was applied to detect MMP13 protein expression. Soluble sGAG secretion/ formation was analysed by the dimethylmethylene blue (DMMB) assay. lncRNA-CIR overexpression or inhibition was performed using overexpression plasmid and small interfering RNAs (siRNAs), respectively. Results: lncRNA-CIR significantly up-regulated in OA patients, concomitantly down-regulated miR-27 and up-regulated MMP13. Bioinformatics analysis predicted miR-27 was the target of both lncRNA-CIR and MMP13. Overexpression of lncRNA-CIR significantly increased the expression of MMP13, while miR-27 remarkably suppressed the expression of MMP13, Accompanying with the increases of mRNA level, protein level and relative luciferase activity. Conclusion: The present findings indicated that lncRNA-CIR/miR-27/MMP13 axis involved in the degradation of the ECM of chondrocyte in OA.

MiR‐27 prevents atherosclerosis by inhibiting inflammatory responses induced by lipoprotein lipase. Overexpression of miR‐27b attenuates angiotensin‐induced atrial fibrosis. Nevertheless, studies have rarely investigated on the effect of miR‐27 in cardiomyocyte injury. H9c2 cells were transfected with miR‐27 mimic/inhibitor. Then the cell proliferation was tested by MTT assay and the cell apoptosis was detected by flow cytometry. The luciferase activity assay was utilized to analyze the relationship between miR‐27 and TGFBR1. Quantificational real‐time polymerase chain reaction and western blot were utilized to detect the cardiomyocyte differentiation marker and nuclear factor kappa B (NF‐κB) pathway. Our outcomes demonstrated that miR‐27 expression was downregulated cardiomyocyte injury subjected to hypoxia/reoxygenation (H/R). Additionally, overexpression of miR‐27 could significantly alleviate cardiomyocyte injury by regulating cell activity and apoptosis. The luciferase activity assay confirmed that transforming growth factor ß receptor 1 (TGFBR1) is a direct hallmark of miR‐27. Besides, overexpression of miR‐27 promoted the expression of TGFBR1 in H/R model. After transfection with miR‐27 mimic/inhibitor, the expression of NF‐κB pathway‐related proteins was decreased/increased. Taken together, our data manifested that miR‐27 repressed cardiomyocyte injury induced by H/R via mediating TGFBR1 and inhibiting NF‐κB signaling pathway. Furthermore, miR‐27/ TGFBR1 might be utilized as hopeful biomarkers for myocardial ischemia diagnosis and treatment.

Multiple myeloma (MM) is an incurable hematological malignancy characterized by abnormal infiltration of plasma cells in the bone marrow. MicroRNAs (miRNAs) have emerged as crucial regulators in human tumorigenesis and tumor progression. miR-27, a novel cancer-related miRNA, has been confirmed to be implicated in multiple types of human tumors; however, its biological role in MM remains largely unknown. The present study aimed to characterize the biological role of miR-27 in MM and elucidate the potential molecular mechanisms. Here we found that miR-27 was significantly up-regulated in MM samples compared with normal bone marrow samples from healthy donors. Moreover, the log-rank test and Kaplan–Meier survival analysis displayed that MM patients with high miR-27 expression experienced a significantly shorter overall survival than those with low miR-27 expression. In the current study, we transfected MM cells with miR-27 mimics or miR-27 inhibitor to manipulate its expression. Functional studies demonstrated that miR-27 overexpression promoted MM cell proliferation, facilitated cell cycle progression, and expedited cell migration and invasion; whereas miR-27 knockdown inhibited cell proliferation, induced cell cycle arrest, and slowed down cell motility. Mechanistic studies revealed that Sprouty homolog 2 (SPRY2) was a direct target of miR-27 and that rescuing SPRY2 expression reversed the promoting effects of miR-27 on MM cell proliferation, migration, and invasion. Besides, miR-27 ablation suppressed tumorigenecity of MM cells in mouse xenograft models. Collectively, our data indicate that miR-27 exerts its oncogenic functions in MM by targetting SPRY2 and that miR-27 may be used as a promising candidate target in MM treatment.

To disclose the mechanisms surrounding obesity, we selected microRNAs (miRNAs) that target genes involved in adipogenesis, angiogenesis, and inflammation and compared their expression levels in the subcutaneous adipose tissue of 40 obese and nonobese women. Mature miRNAs were extracted from subcutaneous adipose tissue samples that were collected during surgery and quantified by real-time polymerase chain reaction. miR-16 was overexpressed in the nonobese group (n-expression ratio = − 151.1; P

The negative role of the activated stimulator of IFN genes (STING) has been uncovered in autoinflammatory disease and cancer. However, the role of STING in virus-related carcinogenesis is not well known. Herein, HPV(+) tongue squamous cell carcinoma (TSCC) (n=25) and HPV(-) TSCC samples (n=25) were randomly collected and were verified by in situ hybridization (ISH) and p16 immunohistochemistry (IHC) to assess the expression and activated status of STING through IHC. The results showed that the expression of STING was up-regulated during the development of TSCC. Interestingly, although the expression of STING showed no difference between HPV(+/-) TSCC samples, the activated status of STING with dark staining around the nucleus was observed in HPV(+) TSCC samples. The role of activated STING was analyzed in three cell lines by siRNA and indicated that activated STING had no impact on cell viability or apoptosis but promoted the induction of several immunosuppressive cytokines, e.g., IL-10, IDO and CCL22, which facilitated the infiltration of regulatory T cells (Tregs). Moreover, increased infiltration of Foxp3(+) Tregs along with increased expression of CCL22 was confirmed in HPV(+) TSCC samples. An inhibitor of the MAPK/AP-1 pathway (U0126) and the silencing of c-jun significantly suppressed CCL22 induction and the recruitment of Tregs by activated STING. Furthermore, down-regulated miR-27 was verified in independent fresh TSCC samples (n=50) and eight cell lines, which enhanced STING activation and led to increased CCL22 expression for Tregs recruitment in the TSCC microenvironment. Therefore, our findings provided distinct insight into the side effects of activated STING in HPV-related carcinogenesis.

miR-27 plays a negative role in the regulation of adipogenesis. However, the molecular mechanism still remains to be clarified. In the present study, we found that miR-27 inhibits adipogenesis partially by repressing the early adipogenic transcription factor cAMP response element-binding protein by directly targeting its 3' untranslated region. In addition, we demonstrated that tumor necrosis factor-α (TNF-α) treatment up-regulates miR-27 through the NF-κB pathway. Furthermore, anti-miR-27 reduces the TNF-α-induced inhibition of adipogenesis. Simultaneously, the levels of miR-27 expression were decreased in mature adipocytes of obese mice when compared with lean mice. Our data revealed a novel mechanism of miR-27 in the regulation of adipogenesis.

Atherosclerosis (As) is now widely appreciated to represent a chronic inflammatory reaction of the vascular wall in response to dyslipidemia and endothelial distress involving the inflammatory recruitment of leukocytes and the activation of resident vascular cells. MicroRNAs (miRNAs) are a group of endogenous, small (~22 nucleotides in length) non-coding RNA molecules, which function specifically by base pairing with mRNA of genes, thereby induce translation repressions of the genes within metazoan cells. Recently, the function of miR-27, one of the miRNAs, in the initiation and progression of atherosclerosis has been identified. In vivo and in vitro studies suggest that miR-27 may serve as a diagnostic and prognostic marker for atherosclerosis. More recently, studies have identified important roles for miR-27 in angiogenesis, adipogenesis, inflammation, lipid metabolism, oxidative stress, insulin resistance and type 2 diabetes, etc. In this review, we focus on the role of miR-27 in the development of vulnerable atherosclerotic plaques, potential as a disease biomarker and novel therapeutic target in atherosclerosis.

MicroRNAs (miRNAs) are involved in a plethora of important biological processes, from embryonic development to homeostasis in adult tissues. Recently, miRNAs have emerged as a class of epigenetic regulators of metabolism and energy homeostasis. We have investigated the role of miRNAs in the regulation of adipogenic differentiation. In this article, we demonstrate that the miR-27 gene family is downregulated during adipogenic differentiation. Overexpression of miR-27 specifically inhibited adipocyte formation, without affecting myogenic differentiation. We also found that expression of miR-27 resulted in blockade of expression of PPARgamma and C/EBPalpha, the two master regulators of adipogenesis. Importantly, expression of miR-27 was increased in fat tissue of obese mice and was regulated by hypoxia, an important extracellular stress associated with obesity. Our data strongly suggest that miR-27 represents a new class of adipogenic inhibitors and may play a role in the pathological development of obesity.

MicroRNAs are noncoding RNAs of approximately 22–24 nucleotides which are capable of interacting with the 3′ untranslated region of coding RNAs (mRNAs), leading to mRNA degradation and/or protein translation blockage. In recent years, differential microRNA expression in distinct cardiac development and disease contexts has been widely reported, yet the role of individual microRNAs in these settings remains largely unknown. We provide herein evidence of the role of miR-27 and miR-125 regulating distinct muscle-enriched transcription factors. Overexpression of miR-27 leads to impair expression ofMstnandMyocdin HL1 atrial cardiomyocytes but not in Sol8 skeletal muscle myoblasts, while overexpression of miR-125 resulted in selective upregulation ofMef2din HL1 atrial cardiomyocytes and downregulation in Sol8 cells. Taken together our data demonstrate that a single microRNA, that is, miR-27 or miR-125, can selectively upregulate and downregulate discrete number of target mRNAs in a cell-type specific manner.

MicroRNAs (miRNAs) play an essential role in regulating cell differentiation either by inhibiting mRNA translation or by inducing its degradation. However, the role of miRNAs in odontoblastic cell differentaion is largely unknown. In the present study, we demonstrate that the expression of miR-27 was significantly increased during MDPC-23 odontoblastic cell differentiation. Furthermore, the up-regulation of miR-27 promotes the differentiation of MDPC-23 odontoblastic cells and accelerates mineralization without cell proliferation. In addition, our results of target gene prediction revealed that the mRNA of adenomatous polyposis coli (APC) associated with Wnt/β-catenin signaling pathway has miR-27 binding site in the its 3' UTR and is suppressed by miR-27. Subsequentially, the down-regulated APC by miR-27 triggered the activation of Wnt/β-catenin signaling through accumulation of β-catenin in the nucleus. Our data suggest that miR-27 promotes MDPC-23 odontoblastic cell differentiation by targeting APC and activating Wnt/β-catenin signaling. Therefore, miR-27 might be considered a critical candidate as an odontoblastic differentiation molecular target for the development of miRNA based therapeutic agents in the dental medicine.

MiRNAs are small non-coding RNAs that significantly regulate the translation of protein coding genes in higher organisms. MicroRNAs are involved in almost every biological process, including early development, lineage commitment, growth and differentiation, cell death, and metabolic control. Misregulation of miRNAs belonging to the intergenic miR-23a-miR-27a-miR-24-2 cluster has been recently associated to cardiac and skeletal muscle diseases, and they are up-regulated in hypertrophic cardiomyopathy and skeletal muscle atrophy. Despite these facts, the basal transcriptional regulation of miR-23a/miR-27-a/miR-24-2 cluster and how it is altered under pathological conditions remain unclear. In this study, we identified and functionally characterized conserved upstream and downstream regulatory sequences from the miR-23a-miR-27a-miR-24-2 locus that are implicated on its transcriptional control. Our data demonstrate that Srf plays a pivotal role in modulating miR-23a-miR-27a-miR-24-2 cluster proximal promoter activity. Importantly, pro-hypertrophic signalling pathways such as those driven by angiotensin II and norepinephrine also regulate miR-23a-miR-27a-miR-24-2 cluster proximal promoter activity. Taking together, our results provide new insights into the regulatory networks driving miR-23a-miR-27a-miR-24-2 cluster expression in cardiac and skeletal muscles.

BackgroundMicroRNA-27a (miR-27a) is thought to be an onco-microRNA that promotes tumor growth and metastasis by downregulating ZBTB10. The potential predictive value of miR-27a was studied in breast cancer patients.MethodsThe expression of miR-27a and ZBTB10 was examined in 102 breast cancer cases using in situ hybridization (ISH) and immunohistochemistry techniques and were evaluated semi-quantitatively by examining the staining index. The Correlation of miR-27a and ZBTB10 expression was analyed by Spearman Rank Correlation. The association of miR-27a and ZBTB10 expression with clinicopathological characteristics was analyzed using the χ(2) test, and their effects on patient survival were analyzed by a log-rank test and the Kaplan-Meier method. Univariate and multivariate Cox regression analyses were used to evaluate the prognostic values of miR-27a and ZBTB10.ResultsmiR-27a was markedly up-regulated in invasive breast cancers that expressed low levels of ZBTB10 (PConclusionsHigh miR-27a expression is associated with poor overall survival in patients with breast cancer, which suggests that miR-27a could be a valuable marker of breast cancer progression.

MicroRNAs (miRNAs) are small non-coding RNAs that control expression of complementary target mRNAs. A growing number of miRNAs has been implicated in the pathogenesis of cardiac diseases, mostly based not on functional data, but on the observation that they are dysregulated in diseased myocardium. Consequently, our knowledge regarding a potential cardiac role of the majority of miRNAs is limited. Here, we report the development of an assay format that allows the simultaneous analysis of several hundred molecules with regard to their phenotypic effect on primary rat cardiomyocytes. Using automated microscopy and an edge detection algorithm, this assay achieved high reproducibility and a robust assessment of cardiomyocyte size as a key parameter. Screening a library of synthetic miRNAs revealed several miRNAs previously not recognized as pro- or anti-hypertrophic. Out of these, we selected nine miRNAs and confirmed the pro-hypertrophic potential of miR-22, miR-30c, miR-30d, miR-212, miR-365 and the anti-hypertrophic potential of miR-27a, miR-27b and miR-133a. Quantitative analysis of the expression level of pro-hypertrophic miRNAs in primary cardiomyocytes indicated a rather low level of correlation of the phenotypic effects of individual miRNAs and their expression level. This assay allows the automated determination of cell size in primary cardiomyocytes and permitted the identification of a set of miRNAs capable of regulating cardiomyocyte hypertrophy. Elucidating their mechanism of action should provide insight into mechanisms underlying the cardiomyocyte hypertrophic response. This article is part of a Special Issue entitled ‘Possible Editorial’.

Canonical Wnt signaling is particularly important for differentiation of human mesenchymal stem cells into osteoblast. MicroRNAs (miRNAs) also play an essential role in regulating cell differentiation. However, the role of miRNAs in osteoblast differentiation remains poorly understood. Here we found that the expression of miR-27 was increased during hFOB1.19 cells differentiation. Moreover, ectopic expression of miR-27 promoted hFOB1.19 cells differentiation, whereas its repression was sufficient to inhibit cell differentiation. Western blot analysis showed that the expression level of miR-27 was positively correlated with that of β-catenin, a key protein in Wnt signaling. Further, we verified that miR-27 directly targeted and inhibited adenomatous polyposis coli (APC) gene expression, and activated Wnt signaling through accumulation of β-catenin. This study suggests miR-27 is an important mediator of osteoblast differentiation, thus offering a new target for the development of preventive or therapeutic agents against osteogenic disorders.