Endovascular treatment of intracranial aneurysms: Past and present.

Intracranial aneurysm is common in stroke and, once rupturing, will cause disaster to patients. Nowadays, endovascular treatment has become a routine to reduce the risk of intracranial aneurysms rupture. Successive endovascular methods, like balloon-assisted coiling, stent-assisted coiling, and flow diversion, have become new choices for doctors.

IntS6 and the Integrator phosphatase module tune the efficiency of select premature transcription termination events.

The metazoan-specific Integrator complex catalyzes 3' end processing of small nuclear RNAs (snRNAs) and premature termination that attenuates the transcription of many protein-coding genes. Integrator has RNA endonuclease and protein phosphatase activities, but it remains unclear if both are required for complex function. Here, we show IntS6 (Integrator subunit 6) over-expression blocks Integrator function at a subset of Drosophila protein-coding genes, although having no effect on snRNAs or attenuation of other loci.

CRISPR/Cas13 effectors have differing extents of off-target effects that limit their utility in eukaryotic cells.

CRISPR/Cas13 effectors have garnered increasing attention as easily customizable tools for detecting and depleting RNAs of interest. Near perfect complementarity between a target RNA and the Cas13-associated guide RNA is required for activation of Cas13 ribonuclease activity. Nonetheless, the specificity of Cas13 effectors in eukaryotic cells has been debated as the Cas13 nuclease domains can be exposed on the enzyme surface, providing the potential for promiscuous cleavage of nearby RNAs (so-called collateral damage).

Expression and related mechanisms of miR-330-3p and S100B in an animal model of cartilage injury.

Objective: To investigate the roles of and relationship between microRNA (miR)-330-3p and S100 calcium-binding protein B (S100B) in an animal model of cartilage injury.

Methods: This study included 30 New Zealand male rabbits randomly divided into three groups: an intervention group, a model group and a sham surgery control group. Modelling was performed in the intervention and model groups, but in the sham surgery group, only the skin was cut.

Use of circular RNAs as markers of readthrough transcription to identify factors regulating cleavage/polyadenylation events.

Circular RNAs with covalently linked ends are generated from many eukaryotic protein-coding genes when the pre-mRNA splicing machinery backsplices. These mature transcripts are resistant to digestion by exonucleases and typically have much longer half-lives than their associated linear mRNAs. Circular RNAs thus have great promise as sensitive biomarkers, including for detection of transcriptional activity.

RNAi Screening to Identify Factors That Control Circular RNA Localization.

Thousands of eukaryotic protein-coding genes are noncanonically spliced to generate circular RNAs that have covalently linked ends. These transcripts are resistant to degradation by exonucleases, which enables some to accumulate to higher levels than the associated linear mRNA. In general, exonic circular RNAs accumulate in the cytoplasm, but functions for most of these transcripts remain unknown.

Author Correction: Circular RNA CircFndc3b modulates cardiac repair after myocardial infarction via FUS/VEGF-A axis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Circular RNA CircFndc3b modulates cardiac repair after myocardial infarction via FUS/VEGF-A axis.

Circular RNAs are generated from many protein-coding genes, but their role in cardiovascular health and disease states remains unknown. Here we report identification of circRNA transcripts that are differentially expressed in post myocardial infarction (MI) mouse hearts including circFndc3b which is significantly down-regulated in the post-MI hearts. Notably, the human circFndc3b ortholog is also significantly down-regulated in cardiac tissues of ischemic cardiomyopathy patients.

The Integrator complex cleaves nascent mRNAs to attenuate transcription.

Cellular homeostasis requires transcriptional outputs to be coordinated, and many events post-transcription initiation can dictate the levels and functions of mature transcripts. To systematically identify regulators of inducible gene expression, we performed high-throughput RNAi screening of the Metallothionein A (MtnA) promoter. This revealed that the Integrator complex, which has a well-established role in 3' end processing of small nuclear RNAs (snRNAs), attenuates MtnA transcription during copper stress.

Ribosome queuing enables non-AUG translation to be resistant to multiple protein synthesis inhibitors.

Aberrant translation initiation at non-AUG start codons is associated with multiple cancers and neurodegenerative diseases. Nevertheless, how non-AUG translation may be regulated differently from canonical translation is poorly understood. Here, we used start codon-specific reporters and ribosome profiling to characterize how translation from non-AUG start codons responds to protein synthesis inhibitors in human cells.

A length-dependent evolutionarily conserved pathway controls nuclear export of circular RNAs.

Circular RNAs (circRNAs) are generated from many protein-coding genes. Most accumulate in the cytoplasm, but how circRNA localization or nuclear export is controlled remains unclear. Using RNAi screening, we found that depletion of the DExH/D-box helicase Hel25E results in nuclear accumulation of long (>800-nucleotide), but not short, circRNAs.

The Output of Protein-Coding Genes Shifts to Circular RNAs When the Pre-mRNA Processing Machinery Is Limiting.

Many eukaryotic genes generate linear mRNAs and circular RNAs, but it is largely unknown how the ratio of linear to circular RNA is controlled or modulated. Using RNAi screening in Drosophila cells, we identify many core spliceosome and transcription termination factors that control the RNA outputs of reporter and endogenous genes. When spliceosome components were depleted or inhibited pharmacologically, the steady-state levels of circular RNAs increased while expression of their associated linear mRNAs concomitantly decreased.

Inducible Expression of Eukaryotic Circular RNAs from Plasmids.

Thousands of eukaryotic protein-coding genes are noncanonically spliced to generate circular RNAs. Because they have covalently linked ends, circular RNAs are resistant to degradation by exonucleases and some accumulate to higher levels than their associated linear mRNAs. The functions of most circular RNAs are still unknown, but recent work has revealed key insights into how the pre-mRNA splicing machinery catalyzes backsplicing.

Combinatorial control of Drosophila circular RNA expression by intronic repeats, hnRNPs, and SR proteins.

Thousands of eukaryotic protein-coding genes are noncanonically spliced to produce circular RNAs. Bioinformatics has indicated that long introns generally flank exons that circularize in Drosophila, but the underlying mechanisms by which these circular RNAs are generated are largely unknown. Here, using extensive mutagenesis of expression plasmids and RNAi screening, we reveal that circularization of the Drosophila laccase2 gene is regulated by both intronic repeats and trans-acting splicing factors.

AMPK-HDAC5 pathway facilitates nuclear accumulation of HIF-1α and functional activation of HIF-1 by deacetylating Hsp70 in the cytosol.

Hypoxia-inducible factor 1 (HIF-1) transcriptionally promotes production of adenosine triphosphate (ATP) whereas AMPK senses and regulates cellular energy homeostasis. A histone deacetylase (HDAC) activity has been proven to be critical for HIF-1 activation but the underlying mechanism and its role in energy homesostasis remain unclear. Here, we demonstrate that HIF-1 activation depends on a cytosolic, enzymatically active HDAC5.

Short intronic repeat sequences facilitate circular RNA production.

Recent deep sequencing studies have revealed thousands of circular noncoding RNAs generated from protein-coding genes. These RNAs are produced when the precursor messenger RNA (pre-mRNA) splicing machinery "backsplices" and covalently joins, for example, the two ends of a single exon. However, the mechanism by which the spliceosome selects only certain exons to circularize is largely unknown.

SHBG is an important factor in stemness induction of cells by DHT in vitro and associated with poor clinical features of prostate carcinomas.

Androgen plays a vital role in prostate cancer development. However, it is not clear whether androgens influence stem-like properties of prostate cancer, a feature important for prostate cancer progression. In this study, we show that upon DHT treatment in vitro, prostate cancer cell lines LNCaP and PC-3 were revealed with higher clonogenic potential and higher expression levels of stemness related factors CD44, CD90, Oct3/4 and Nanog.

Notch1 is a 5-fluorouracil resistant and poor survival marker in human esophagus squamous cell carcinomas.

Notch signaling involves the processes that govern cell proliferation, cell fate decision, cell differentiation and stem cell maintenance. Due to its fundamental role in stem cells, it has been speculated during the recent years that Notch family may have critical functions in cancer stem cells or cancer cells with a stem cell phenotype, therefore playing an important role in the process of oncogenesis. In this study, expression of Notch family in KYSE70, KYSE140 and KYSE450 squamous esophageal cancer cell lines and virus transformed squamous esophageal epithelial cell line Het-1A was examined by quantitative RT-PCR.

Glutamine depletion and glucose depletion trigger growth inhibition via distinctive gene expression reprogramming.

Glutamine (Gln) and glucose (Glc) represent two important nutrients for proliferating cells, consistent with the observations that oncogenic processes are associated with enhanced glycolysis and glutaminolysis. Gln depletion and Glc depletion have been shown to trigger growth arrest and eventually cell death. Solid tumors often outgrow the blood supply, resulting in ischemia, which is associated with hypoxia and nutrient insufficiency.

The hypoxic microenvironment upgrades stem-like properties of ovarian cancer cells.

Background: To study whether hypoxia influences the stem-like properties of ovarian cancer cells and their biological behavior under hypoxia.

Method: Ovarian cancer cell lines ES-2 and OVCAR-3 were cultivated in different oxygen tensions for proliferation, cell cycling and invasion analyses. The clonogenic potential of cells was examined by colony formation and sphere formation assays.

Synergistic effect of SCF and G-CSF on stem-like properties in prostate cancer cell lines.

Bone marrow metastases are formed in the late phases of prostate cancer disease. Stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) are present in the microenvironment of the bone marrow and play a vital role in cell biology therein. The present study was to investigate the influence of SCF and G-CSF on stem-like properties in prostate cancer cell lines.

Prostate cancer cell lines under hypoxia exhibit greater stem-like properties.

Hypoxia is an important environmental change in many cancers. Hypoxic niches can be occupied by cancer stem/progenitor-like cells that are associated with tumor progression and resistance to radiotherapy and chemotherapy. However, it has not yet been fully elucidated how hypoxia influences the stem-like properties of prostate cancer cells.

Nitrogen anabolism underlies the importance of glutaminolysis in proliferating cells.

Glutaminolysis and Warburg effect are the two most noticeable metabolic features of tumor cells whereas their biological significance in cell proliferation remains elusive. A widely accepted current hypothesis is that tumor cells use glutamine as a preferred carbon source for energy and reducing power, which has been used to explain both glutaminolysis and the Warburg effect. Here we provide evidence to show that supplying nitrogen, not the carbon skeleton, underlies the major biological importance of glutaminolysis for proliferating cells.

Histone deacetylase inhibitors synergize p300 autoacetylation that regulates its transactivation activity and complex formation.

p300/cyclic AMP-responsive element binding protein-binding protein (CBP) are general coactivators for multiple transcription factors involved in various cellular processes. Several highly conserved domains of p300/CBP serve as interacting sites for transcription factors and regulatory proteins. Particularly, the intrinsic histone acetyltransferase (HAT) activity and transactivation domains (TAD) play essential roles for their coactivating function.

Effects of histone deacetylase inhibitors on HIF-1.

Hypoxia inducible factors (HIF) are the master transcriptional regulators of angiogenesis and energy metabolism in mammals. Histone deacetylase inhibitors (HDAIs) are among the promising anti -cancer compounds currently in clinical trials. In addition to inducing hyperacetylation of histones, HDAIs have been found to repress HIF function, which has been construed as an important pharmacological mechanism underlying the HDAI -mediated repression of tumor growth and angiogenesis.