Intracellular accumulation of the abnormally modified tau is hallmark pathology of Alzheimer's disease (AD), but the mechanism leading to tau aggregation is not fully characterized. Here, we studied the effects of tau SUMOylation on its phosphorylation, ubiquitination, and degradation. We show that tau SUMOylation induces tau hyperphosphorylation at multiple AD-associated sites, whereas site-specific mutagenesis of tau at K340R (the SUMOylation site) or simultaneous inhibition of tau SUMOylation by ginkgolic acid abolishes the effect of small ubiquitin-like modifier protein 1 (SUMO-1). Conversely, tau hyperphosphorylation promotes its SUMOylation; the latter in turn inhibits tau degradation with reduction of solubility and ubiquitination of tau proteins. Furthermore, the enhanced SUMO-immunoreactivity, costained with the hyperphosphorylated tau, is detected in cerebral cortex of the AD brains, and β-amyloid exposure of rat primary hippocampal neurons induces a dosedependent SUMOylation of the hyperphosphorylated tau. Our findings suggest that tau SUMOylation reciprocally stimulates its phosphorylation and inhibits the ubiquitination-mediated tau degradation, which provides a new insight into the AD-like tau accumulation.is the most common neurodegenerative disorder in the elderly. Intracellular accumulation of neurofibrillary tangles (NFTs) and extracellular precipitation of senile plaques are the most prominent pathological hallmarks of AD (1-3). The clinical-to-pathological correlation studies have demonstrated that the number of NFTs consisting of hyperphosphorylated tau correlates with the degree of dementia in AD (4-6). Tau is the major microtubule-associated protein that normally contains 2-3 mol of phosphate per mole of tau protein.In AD brains, tau is abnormally hyperphosphorylated (namely AD-P-tau) and the phosphate level increases to 5-9 mol phosphate per mole tau (4). AD-P-tau does not bind to tubulin and become incompetent in promoting microtubule assembly and maintaining the stability of the microtubules. The AD-P-tau also sequesters normal tau from microtubules (7), and serves as a template for the conversion of normal tau into misfolded protein in a prion-like manner (8). In addition to hyperphosphorylation, tau is also contains other posttranslational modifications, such as ubiquitination and SUMOylation (5, 9-11). The abnormal modification of tau also decreases its solubility, and ∼40% of the hyperphosphorylated tau in AD brains has been isolated as sedimentable nonfibril cytosolic protein (1, 12). Although the mechanisms underlying the formation of the NFTs remain unclear, the altered tau modifications and impaired degradation are believed to play a role. Therefore, clarifying the mechanism that may cause tau accumulation is of great significance for understanding the pathogenesis of AD and for developing new therapeutics.Like other proteins, tau can be degraded by autophagy-lysosomal and ubiqutin-proteasomal systems under physiological conditions. In mouse cortical neurons, a C-terminal-trunca...

The management of PCa in China differs from that in Western countries. To date surgical castration represents standard treatment. Screening detection of PCa could help detect earlier stage tumors and improve the outcome in patients.

Non-small cell lung cancer (NSCLC) is the major cause of cancer death worldwide. Increasing evidence shows that microRNAs (miRNAs), evolutionally conserved non-coding RNAs, are widely involved in the development and progression of NSCLC. Aberrant alteration of miRNAs expression has been implicated in NSCLC initiation and progression. Herein, we studied the role of miR-27b in NSCLC cells. We found that miR-27b was significantly decreased in several NSCLC cell lines. Forced overexpression of miR-27 inhibited both the growth and invasion of NSCLC cells. Furthermore, we identified Sp1 transcription factor (Sp1) as a target of miR-27b in NSCLC cells. Moreover, we found that miR-27 suppressed growth and invasion of NSCLC cells partially by targeting Sp1. Our data indicate that miR-27b may play a critical role in the development of NSCLC.

Because of its high pathogenicity and infectivity, tuberculosis is a serious threat to human health. Some information about the functions of the genes in Mycobacterium tuberculosis genome was currently available, but it was not enough to explore transcriptional regulatory mechanisms. Here, we applied the WGCNA (Weighted Gene Correlation Network Analysis) algorithm to mine pooled microarray datasets for the M. tuberculosis H37Rv strain. We constructed a co-expression network that was subdivided into 78 co-expression gene modules. The different response to two kinds of vitro models (a constant 0.2% oxygen hypoxia model and a Wayne model) were explained based on these modules. We identified potential transcription factors based on high Pearson’s correlation coefficients between the modules and genes. Three modules that may be associated with hypoxic stimulation were identified, and their potential transcription factors were predicted. In the validation experiment, we determined the expression levels of genes in the modules under hypoxic condition and under overexpression of potential transcription factors (Rv0081, furA (Rv1909c), Rv0324, Rv3334, and Rv3833). The experimental results showed that the three identified modules related to hypoxia and that the overexpression of transcription factors could significantly change the expression levels of genes in the corresponding modules.

Abnormal tau hyperphosphorylation is an early pathological marker of Alzheimer’s disease (AD), however, the upstream factors that regulate tau phosphorylation are not illustrated and there is no efficient strategy to arrest tau hyperphosphorylation. Here, we find that activation of endogenous EphB2 receptor by ligand stimulation (ephrinB1/Fc) or by ectopic expression of EphB2 plus the ligand stimulation induces a remarkable tau dephosphorylation at multiple AD-associated sites in SK-N-SH cells and human embryonic kidney cells that stably express human tau (HEK293-tau). In cultured hippocampal neurons and the hippocampus of human tau transgenic mice, dephosphorylation of tau proteins was also detected by stimulation of EphB2 receptor. EphB2 activation inhibits glycogen synthase kinase-3β (GSK-3β), a crucial tau kinase, and activates phosphatidylinositol-3-kinase (PI3K)/Akt both in vitro and in vivo, whereas simultaneous inhibition of PI3K or upregulation of GSK-3β abolishes the EphB2 stimulation-induced tau dephosphorylation. Finally, we confirm that ephrinB1/Fc treatment induces tyrosine phosphorylation (activation) of EphB2, while deletion of the tyrosine kinase domain (VM) of EphB2 eliminates the receptor stimulation-induced GSK-3β inhibition and tau dephosphorylation. We conclude that activation of EphB2 receptor kinase arrests tau hyperphosphorylation through PI3K-/Akt-mediated GSK-3β inhibition. Our data provide a novel membranous target to antagonize AD-like tau pathology.

Non-coding RNA (ncRNA) is abundant in plant genomes, but is poorly described with unknown functionality in most species. Using whole genome RNA sequencing, we identified 1885, 1910 and 1299 lncRNAs and 186, 157 and 161 miRNAs at the whole genome level in the three Brassica species B. napus, B. oleracea and B. rapa, respectively. The lncRNA sequences were divergent between the three Brassica species. One quarter of lncRNAs were located in tandem repeat (TR) region. The expression of both lncRNAs and miRNAs was strongly biased towards the A rather than the C subgenome in B. napus, unlike mRNA expression. miRNAs in genic regions had higher average expression than miRNAs in non-genic regions in B. napus and B. oleracea. We provide a comprehensive reference for the distribution, functionality and interactions of lncRNAs and miRNAs in Brassica.

Background Although rapeseed ( Brassica napus L.) mutant forming multiple siliques was morphologically described and considered to increase the silique number per plant, an important agronomic trait in this crop, the molecular mechanism underlying this beneficial trait remains unclear. Here, we combined bulked-segregant analysis (BSA) and whole genome re-sequencing (WGR) to map the genomic regions responsible for the multi-silique trait using two pools of DNA from the near-isogenic lines (NILs) zws-ms (multi-silique) and zws-217 (single-silique). We used the Euclidean Distance (ED) to identify genomic regions associated with this trait based on both SNPs and InDels. We also conducted transcriptome sequencing to identify differentially expressed genes (DEGs) between zws-ms and zws-217. Results Genetic analysis using the ED algorithm identified three SNP- and two InDel-associated regions for the multi-silique trait. Two highly overlapped parts of the SNP- and InDel-associated regions were identified as important intersecting regions, which are located on chromosomes A09 and C08, respectively, including 2044 genes in 10.20-MB length totally. Transcriptome sequencing revealed 129 DEGs between zws-ms and zws-217 in buds, including 39 DEGs located in the two abovementioned associated regions. We identified candidate genes involved in multi-silique formation in rapeseed based on the results of functional annotation. Conclusions This study identified the genomic regions and candidate genes related to the multi-silique trait in rapeseed. Electronic supplementary material The online version of this article (10.1186/s12864-019-5675-4) contains supplementary material, which is available to authorized users.

miR-141 belongs to the miR-200 family, and has been found to be associated with numerous human malignancies; however, its role in gastric cancer (GC) has not been examined in detail. Here, we validated that miR-141 was decreased in GC tissues and cell lines. Forced expression of miR-141 significantly repressed GC cell proliferation and colony formation. Furthermore, miR-141 suppressed in vitro migration and invasion of GC cells. Hepatoma-derived growth factor (HDGF) was confirmed to be a direct target of miR-141 in GC cells. The suppressive effects of miR-141 on GC cell proliferation, colony formation, in vitro migration, and invasion were partially mediated by suppressing HDGF expression. Moreover, the expression of HDGF was negatively correlated with miR-141 in GC tissues. Our data suggest that miR-141 might be associated and plays essential role in GC progression.