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Nuclear paraspeckles assembly transcript 1 (NEAT1) is a well-known long noncoding RNA (lncRNA) with various functions in different physiological and pathological processes. Notably, aberrant NEAT1 expression is implicated in the pathogenesis of various neurodegenerative diseases, including Alzheimer's disease (AD). However, the molecular mechanism of NEAT1 in AD remains poorly understood. In this study, we investigated that NEAT1 regulated microtubules (MTs) polymerization via FZD3/GSK3β/p-tau pathway. Downregulation of NEAT1 inhibited Frizzled Class Receptor 3 (FZD3) transcription activity by suppressing H3K27 acetylation (H3K27Ac) at the FZD3 promoter. Our data also demonstrated that P300, an important histone acetyltransferases (HAT), recruited by NEAT1 to bind to FZD3 promoter and mediated its transcription via regulating histone acetylation. In addition, according to immunofluorescence staining of MTs, metformin, a medicine for the treatment of diabetes mellitus, rescued the reduced length of neurites detected in NEAT1 silencing cells. We suspected that metformin may play a neuroprotective role in early AD by increasing NEAT1 expression and through FZD3/GSK3β/p-tau pathway. Collectively, NEAT1 regulates microtubule stabilization via FZD3/GSK3β/P-tau pathway and influences FZD3 transcription activity in the epigenetic way.

In this work, we propose a novel rate control algorithm for Versatile Video Coding (VVC) standard based on its distinct rate-distortion characteristics. By modelling the transform coefficients with the composite Cauchy distribution, higher accuracy compared with traditional distributions has been achieved. Based on the transform coefficient modelling, the theoretically derived R-Q and D-Q models which have been shown to deliver higher accuracy in characterizing RD characteristics for sequences with different content are incorporated into the rate control process. Furthermore, to establish an adaptive bit allocation scheme, the dependency between different levels of frames is modelled by a dependency factor to describe relationship between the reference and to-be-coded frames. Given the derived R-Q and D-Q relationships, as well as the dependency factor, an adaptive bit allocation scheme is developed for optimal bits allocation. We implement the proposed algorithm on VVC Test Model (VTM) 3.0. Experiments show that due to proper bit allocation, for low delay configuration the proposed algorithm can achieve 1.03% BD-Rate saving compared with the default rate control algorithm and 2.96% BD-Rate saving compared with fixed QP scheme. Moreover, 1.29% BD-Rate saving and higher control accuracy have also been observed under the random access configuration.

Endometrial cancer (UCEC) is a complex malignant tumor which remains the third cause of cancer-related death of women. Although UCEC has been repeatedly researched in recent years, the molecular heterogeneity of UCEC made it hard to predict clinical outcomes of this malignant disease. This study was aimed to access the prognostic value of long non-coding RNAs (lncRNAs) in UCEC patients and to identify potential lncRNA biomarker for improving the prognosis and diagnosis of patient. We performed a comprehensive genome-wide analysis of gene expression profiles and clinical data downloaded from The Cancer Genome Atlas (TCGA). After filtering out the differentially expressed genes (DEGs) from expression profiles, the co-expression modules were constructed by weighted gene co-expression network analysis. In the analysis of key modules, four hub genes (TPX2, KIF2C, AURKA and CDCA5) was filtered out, the three hub long non-coding RNAs (ENSG00000258884, ENSG00000274825 and ENSG00000271936) were discovered and verified to be potential prognostic biomarkers.

Nuclear paraspeckles assembly transcript 1 (NEAT1) is a well-known long noncoding RNA (LncRNA) with unclear mechanism in Alzheimer’s disease (AD) progression. Here, we found that NEAT1 down-regulates in the early stage of AD patients and APPswe/PS1dE9 mouse. Moreover, knockdown of NEAT1 induced de-polymerization of microtubule (MT) and axonal retraction of nerve cells by dysregulation of the FZD3/GSK3β/p-tau signaling pathway. Histone acetylation analysis at the Frizzled Class Receptor 3 (FZD3) promoter shows a marked decreased in the levels of the H3K27 acetylation (H3K27Ac) after NEAT1 knockdown. Our data demonstrates that P300/CBP recruited by NEAT1 to the FZD3 promoter and induced its transcription via histone acetylation. In recent years a growing number of evidences have shown an abnormal brain glucose homeostasis in AD. In the present study we also observed an abnormal brain glucose homeostasis and enhanced sirtuin1 (SIRT1) activity after knockdown of NEAT similarly as in AD. Our results provided insight into the role of NEAT1 in the maintenance of MT stability and its effect on glucose metabolism during early stages of AD.

The accumulation of intracellular β-amyloid peptide (Aβ) is important pathological characteristic of Alzheimer’s disease (AD). However, the exact underlying molecular mechanism remains to be elucidated. Here, we reported that Nuclear Paraspeckle Assembly Transcript 1 (NEAT1), a long n on-coding RNA, exhibits repressed expression in the early stage of AD and its down-regulation declines neuroglial cell mediating Aβ clearance via inhibiting expression of endocytosis-related genes. We find that NEAT1 is associated with P300/CBP complex and its inhibition affects H3K27 acetylation (H3K27Ac) and H3K27 crotonylation (H3K27Cro) located nearby to the transcription start site of many genes, including endocytosis-related genes. Interestingly, NEAT1 inhibition down-regulates H3K27Ac but up-regulates H3K27Cro through repression of acetyl-CoA generation. NEAT1 also mediates the binding between STAT3 and H3K27Ac but not H3K27Cro. Therefore, the decrease of H3K27Ac and/or the increase of H3K27Cro declines expression of multiple related genes. Collectively, this study first reveals the different roles of H3K27Ac and H3K27Cro in regulation of gene expression and provides the insight of the epigenetic regulatory mechanism of NEAT1 in gene expression and AD pathology. Electronic supplementary material The online version of this article (10.1007/s00018-019-03074-9) contains supplementary material, which is available to authorized users.