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Summary: Arabidopsis RESISTANCE TO POWDERY MILDEW 8.2 (RPW8.2) is specifically induced by the powdery mildew (PM) fungus (Golovinomyces cichoracearum) in the infected epidermal cells to activate immunity. However, the mechanism of RPW8.2‐induction is not well understood.Here, we identify a G. cichoracearum effector that interacts with RPW8.2, named Gc‐RPW8.2 interacting protein 1 (GcR8IP1), by a yeast two‐hybrid screen of an Arabidopsis cDNA library.GcR8IP1 is physically associated with RPW8.2 with its REALLY INTERESTING NEW GENE finger domain that is essential and sufficient for the association. GcR8IP1 was secreted and translocated into the nucleus of host cell infected with PM. Association of GcR8IP1 with RPW8.2 led to an increase in RPW8.2 in the nucleus. In turn, the nucleus‐localized RPW8.2 promoted the activity of the RPW8.2 promoter, resulting in transcriptional self‐amplification of RPW8.2 to boost immunity at infection sites. Additionally, ectopic expression or host‐induced gene silencing of GcR8IP1 supported its role as a virulence factor in PM.Altogether, our results reveal a mechanism of RPW8.2‐dependent defense strengthening via altered partitioning of RPW8.2 and transcriptional self‐amplification triggered by a PM fungal effector, which exemplifies an atypical form of effector‐triggered immunity. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) play a critical role in the development of cancers. However, the role of miRNAs in glioma is still poorly understood. In this study, we demonstrate that microRNA-10a (miR-10a) promotes cell migration and invasion by negatively regulating the expression of Eph tyrosine kinase receptor A8 ( EphA8 ). Ectopic expression of EphA8 counteracts the promotion of migration and invasion induced by miR-10a. We further demonstrate that miR-10a and EphA8 regulate epithelial–mesenchymal transition (EMT) to affect cell migration and invasion. Collectively, we unveil a branch of the miR-10a/ EphA8 pathway that regulates the progression of glioma. [ABSTRACT FROM AUTHOR]

Objectives To study E2F3a expression and its clinical significance in children with acute lymphoblastic leukemia ( ALL). Methods We quantified E2F3a expression at diagnosis in 148 children with ALL by real-time PCR. In the test cohort ( n = 48), receiver operating characteristic ( ROC) curve was used to find the best cut-off point to divide the patients into E2F3a low- and high-expression groups. The prognostic significance of E2F3a expression was investigated in the test cohort and confirmed in the validation cohort ( n = 100). The correlations of E2F3a expression with the clinical features and treatment outcome of these patients were analyzed. Results ROC curve analysis indicated that the best cut-off point of E2F3a expression was 0.3780. In the test cohort, leukemia-free survival ( LFS) and event-free survival ( EFS) of the low-expression group were lower than those of the high-expression group (log rank: P = 0.026 for both). This finding was verified in the validation cohort. LFS, EFS, and overall survival were also lower in the low-expression group than in the high-expression group (log rank, P = 0.015, 0.008, and 0.002 respectively). E2F3a low expression was correlated with the existence of BCR- ABL fusion. An algorithm composed of E2F3a expression and minimal residual disease ( MRD) could predict relapse or induction failure more precisely than current risk stratification. These results were still significant in the ALL patients without BCR- ABL fusion. Conclusions Low expression of E2F3a was associated with inferior prognosis in childhood ALL. An algorithm composed of E2F3a expression and MRD could predict relapse or induction failure more precisely than that of the current risk stratification. [ABSTRACT FROM AUTHOR]

The selection of suitable reference genes (RGs) for data normalization is a crucial step for obtaining reliable results from gene expression analysis using the quantitative real‐time polymerase chain reaction (qRT‐PCR). Expression stability of eleven putative RGs (miR‐100‐5p, miR‐92a‐3p, miR‐998‐3p, miR‐279d‐3p, miR‐305‐5p, miR‐276a‐3p, miR‐275‐3p, miR‐9a‐5p, miR‐2a‐3p, U6 snRNA and 5S rRNA) was assessed by using a web‐based tool: RefFinder, which integrates four algorithms (Delta Ct, geNorm, NormFinder, and BestKeeper), and the best combination number of RGs was calculated by geNorm. Validation of selected RGs was performed by an expression analysis of let‐7‐5p under different experimental conditions. The best combinations of RGs were shown as follows: miR‐100‐5p + miR‐275‐3p for temperature treatment, miR‐100‐5p + miR‐305‐5p for adult tissues, miR‐276a‐3p + miR‐9a‐5p for genders, miR‐2a‐3p + miR‐276a‐3p for days after eclosion, U6 snRNA + miR‐9a‐5p + miR‐2a‐3p for developmental stages, and U6 snRNA + miR‐279d‐3p for all above conditions, and there was no one RG suitable for all experimental conditions. Incorrect RG selection affected the evaluation of let‐7‐5p abundance. Our findings demonstrate that an integrated approach of multiple algorithms is necessary to identify reliable, stable RGs for miRNA evaluation, and provide a basis for further studies on expression and function analysis of miRNAs and their target genes in Galeruca daurica, a new pest with great outbreaks in Inner Mongolia since 2009. [ABSTRACT FROM AUTHOR]

Mutations in the γ‐secretase complex have been well‐described in familial hidradenitis suppurativa (HS). No gene mutations have been identified in sporadic HS, which comprises 60%–70% of all HS cases. Obesity and smoking are risk factors for HS and are closely related to DNA methylation, an essential epigenetic phenomenon. Hence, we hypothesized that epigenetic modifications might be involved in sporadic HS. To investigate genes with aberrant methylation in sporadic HS cases and assess their expression in skin lesions and blood from patients with HS. Skin lesion samples and corresponding normal skin were obtained from three patients with HS and subjected to whole‐genome DNA methylation sequencing. Blood samples were collected from 20 patients with HS and 20 healthy controls (HCs). The HS mouse model was established by applying tamoxifen to NcstnΔKC mice. Target gene expression was analysed by immunohistochemistry, immunofluorescence, western blotting, enzyme‐linked immunosorbent assay (ELISA) and semiquantitative real‐time polymerase chain reaction (RT‐qPCR). Among 10 807 differentially methylated genes, we filtered 2101 genes with hypermethylated promoter regions, and following bioinformatics analyses, we focused on CXC chemokine ligand 16 (CXCL16). Subsequent functional experiments confirmed the downregulation of CXCL16 and its receptor, CXC chemokine receptor (CXCR) 6, in skin tissue from HS patients and NcstnΔKC mice. Serum CXCL16 concentrations were also significantly decreased in patients with HS. Our data revealed the downregulation of CXCL16 and CXCR6 in HS. [ABSTRACT FROM AUTHOR]

Abstract: Long noncoding RNAs (lncRNAs) have gained extensive attention in recent years, however, their effects on ultraviolet (UV) radiation‐induced skin photodamage remain to be elucidated. In this study, we performed high‐throughput RNA sequencing and comprehensive bioinformatics analyses to characterize the transcriptome profiles including lncRNAs and mRNAs in UVB‐irradiated primary human dermal fibroblasts (HDFs) and to explore the roles of lncRNAs in photoaging. Quantitative reverse transcription–polymerase chain reaction amplification was performed to verify the differentially expressed genes. We subsequently found that knocking down of RP11‐670E13.6, an up‐regulated lncRNA in UVB‐irradiated HDFs, promoted a robust senescence phenotype, including increased numbers of the senescence‐associated β‐galactosidase‐positive cells, decreased cell proliferation, accumulation of cells in G0/G1 phase and a characteristic gene expression signature of senescent cells. In addition, Western blot analysis showed that knocking down of RP11‐670E13.6 activated the p16‐pRB senescence pathway independent of the p53‐p21 pathway. Therefore, we propose that RP11‐670E13.6 may delay cellular senescence in UVB damaged HDFs through the p16‐pRB pathway. [ABSTRACT FROM AUTHOR]

The aim of this study was to identify a microRNA (miRNA) expression signature for predicting HCC (hepatocellular carcinoma) survival. A total of 322 HCC patients in The Cancer Genome Atlas (TCGA) database were randomly divided into training and testing set. miRNAs, associated with survival time in the training set, were identified by using univariate Cox regression analysis. The risk score was formulated based on the expression levels of these miRNAs. Then the miRNA signature was validated in testing set through Kaplan-Meier analysis and log-rank test. hsa-miR-301a, hsa-miR-132, hsa-miR-212, hsa-miR-489, and hsa-miR-1468 were identified to formulate risk score in training set and used to calculate the risk score of each patients in testing set. About 161 patients in testing set were segregated into high- and low-risk group according to the median risk score. The survival time of high-risk group was significantly shorter (p = 0.0248) than low-risk group in testing test. The target genes of five miRNAs were significantly enriched in valine, leucine, and isoleucine degradation pathway and PPAR signaling pathway. hsa-miR-1468 had an up-regulated tendency in HCC tissues compared to adjacent tumor tissues. The expression of hsa-miR-301a, hsa-miR-132, hsa-miR-212, hsa-miR-489, and hsa-miR-1468, which might be potential biomarkers to evaluate HCC patients' prognosis. [ABSTRACT FROM AUTHOR]

Aims Dopamine and glutamate receptors are densely expressed in the nucleus accumbens ( NAc). Active interactions between these receptors contribute to the development of neuropsychiatric diseases, such as drug addiction and relapse. However, the molecular mechanisms underlying these interactions remain unclear. Methods This study established a mouse model of intermittent morphine-induced mouse behavioral sensitization model. Western blot and electrophysiological recording methods were performed to directly identify the affective components of morphine behavioral sensitization. Results Interval morphine administration could cause significant locomotor sensitization. Hyperlocomotion and behavioral locomotor sensitization were significantly suppressed when ifenprodil (5 mg/kg), a selective NR2B subunit-containing N-methyl- d-aspartate ( NMDA) receptor antagonist, or nafadotride (25 μg/kg), a dopamine D3 receptor (D3R)-preferring antagonist, was coadministered with morphine. Western blot analysis showed that morphine behavioral sensitization induced a region-specific increase in phosphorylation of NR2B ( pNR2B) and total levels of NR2B (NR2B) expression in the NAc. Systemically administered nafadotride attenuated behavioral locomotor sensitization induced by morphine and significantly reversed the overexpression of pNR2B and NR2B subunit-containing NMDA receptor in the NAc. NMDA receptor-mediated excitatory postsynaptic currents in the NAc were also significantly reduced by nafadotride. Conclusions These findings suggest that D3Rs are involved in morphine-induced behavioral locomotor sensitization in mice by regulating the NR2B subunits of NMDA receptors in the NAc. [ABSTRACT FROM AUTHOR]