CSTF2 Supports Hypoxia Tolerance in Hepatocellular Carcinoma by Enabling m6A Modification Evasion of PGK1 to Enhance Glycolysis.

Cleavage stimulation factor subunit 2 (CSTF2) is a fundamental factor in the regulation of 3'-end cleavage and alternative polyadenylation of pre-mRNAs. Previous work has identified a tumor-promoting role of CSTF2, suggesting that it may represent a potential therapeutic target. Here, we aimed to elucidate the mechanistic function of CSTF2 in hepatocellular carcinoma (HCC).

Regulations of mA and other RNA modifications and their roles in cancer.

RNA modification is an essential component of the epitranscriptome, regulating RNA metabolism and cellular functions. Several types of RNA modifications have been identified to date; they include N-methyladenosine (mA), N-methyladenosine (mA), 5-methylcytosine (mC), N-methylguanosine (mG), N,2'-O-dimethyladenosine (mA), N-acetylcytidine (acC), etc. RNA modifications, mediated by regulators including writers, erasers, and readers, are associated with carcinogenesis, tumor microenvironment, metabolic reprogramming, immunosuppression, immunotherapy, chemotherapy, etc.

K235 acetylation couples with PSPC1 to regulate the mA demethylation activity of ALKBH5 and tumorigenesis.

N6-methyladenosine (mA) modification plays important roles in bioprocesses and diseases. AlkB homolog 5 (ALKBH5) is one of two mA demethylases. Here, we reveal that ALKBH5 is acetylated at lysine 235 (K235) by lysine acetyltransferase 8 and deacetylated by histone deacetylase 7.

Design, Preparation and In Vitro Evaluation of Core-Shell Fused Deposition Modelling 3D-Printed Verapamil Hydrochloride Pulsatile Tablets.

The aim of the study was to investigate core-shell pulsatile tablets by combining the advantages of FDM 3D printing and traditional pharmaceutical technology, which are suitable for a patient's individual medication and chronopathology. The tablets were designed and prepared with the commercial verapamil hydrochloride tablets as core inside and the fused deposition modelling (FDM) 3D-printed shell outside. Filaments composed of hydroxypropylmethyl cellulose (HPMC) and polyethylenglycol (PEG) 400 were prepared by hot melt extrusion (HME) and used for fabrication of the shell.

FDM 3D-Printed Sustained-Release Gastric-Floating Verapamil Hydrochloride Formulations with Cylinder, Capsule and Hemisphere Shapes, and Low Infill Percentage.

The aim of this work was to design and fabricate fused deposition modeling (FDM) 3D-printed sustained-release gastric-floating formulations with different shapes (cylinder, capsule and hemisphere) and infill percentages (0% and 15%), and to investigate the influence of shape and infill percentage on the properties of the printed formulations. Drug-loaded filaments containing HPMC, Soluplus and verapamil hydrochloride were prepared via hot-melt extrusion (HME) and then used to print the following gastric-floating formulations: cylinder-15, capsule-0, capsule-15, hemisphere-0 and hemisphere-15. The morphology of the filaments and the printed formulations were observed by scanning electron microscopy (SEM).

E3 ligase ZFP91 inhibits Hepatocellular Carcinoma Metabolism Reprogramming by regulating PKM splicing.

Hepatocellular carcinoma (HCC) is one of the most lethal cancers, and few molecularly targeted anticancer therapies have been developed to treat it. Thus, the identification of new therapeutic targets is urgent. Metabolic reprogramming is an important hallmark of cancer.

Small Protein Hidden in lncRNA Promotes "Cancerous" RNA Splicing and Tumorigenesis.

Conventional therapies for late-stage colorectal cancer (CRC) have limited effects because of chemoresistance, recurrence, and metastasis. The "hidden" proteins/peptides encoded by long noncoding RNAs (lncRNAs) may be a novel resource bank for therapeutic options for patients with cancer. Here, lncRNA is discovered to encode a small 130-amino acid protein that interacts with several splicing regulators, such as serine- and arginine-rich splicing factor 3 (SRSF3), to regulate mRNA splicing, and the protein thus is named "Splicing Regulatory Small Protein" (SRSP).

An oncopeptide regulates mA recognition by the mA reader IGF2BP1 and tumorigenesis.

N-methyladenosine (mA) is the most prevalent modification in eukaryotic RNAs. The biological importance of mA relies on mA readers, which control mRNA fate and function. However, it remains unexplored whether additional regulatory subunits of mA readers are involved in the mA recognition on RNAs.

Preparation and In vitro Evaluation of FDM 3D-Printed Ellipsoid-Shaped Gastric Floating Tablets with Low Infill Percentages.

The aim of the study is to investigate the feasibility of fabricating FDM 3D-printed gastric floating tablets with low infill percentages and the effect of infill percentage on the properties of gastric floating tablets in vitro. Propranolol hydrochloride was selected as a model drug, and drug-loaded polyvinyl alcohol (PVA) filaments were produced by hot melt extrusion (HME). Ellipsoid-shaped gastric floating tablets with low infill percentage of 15% and 25% (namely E-15 and E-25) were then prepared respectively by feeding the extruded filaments to FDM 3D printer.

ncRNA-Encoded Peptides or Proteins and Cancer.

Non-coding RNAs (ncRNAs) are unique RNA transcripts that have been widely identified in the eukaryotic genome and have been shown to play key roles in the development of many cancers. However, the rapid development of genome-wide translation profiling and ribosome profiling has revealed that a small number of small open reading frames (sORFs) within ncRNAs actually have peptide- or protein-coding potential. The peptides or proteins encoded by ncRNA (HOXB-AS3, encoded by long ncRNA [lncRNA]; FBXW7-185aa, PINT-87aa, and SHPRH-146aa, encoded by circular RNA [circRNA]; and miPEP-200a and miPEP-200b, encoded by primary miRNAs) have been shown to be critical players in cancer development and progression, through effects upon the regulation of glucose metabolism, the epithelial-to-mesenchymal transition, and the ubiquitination pathway.

Adoptive Transfer of NKG2D CAR mRNA-Engineered Natural Killer Cells in Colorectal Cancer Patients.

By fusing the extracellular domain of the natural killer (NK) cell receptor NKG2D to DAP12, we constructed a chimeric antigen receptor (CAR) to improve NK cell tumor responses. An RNA electroporation approach that provides transient expression of the CAR was adopted as a risk mitigation strategy. Expression of the NKG2D RNA CAR significantly augmented the cytolytic activity of NK cells against several solid tumor cell lines in vitro and provided a clear therapeutic benefit to mice with established solid tumors.

TBC1D8 Amplification Drives Tumorigenesis through Metabolism Reprogramming in Ovarian Cancer.

Cancer cells undergo metabolic reprogramming to support their energy demand and biomass synthesis. However, the mechanisms driving cancer metabolism reprogramming are not well understood. The differential proteins and interacted proteins were identified by proteomics.

Peptides/Proteins Encoded by Non-coding RNA: A Novel Resource Bank for Drug Targets and Biomarkers.

Non-coding RNAs (ncRNAs) are defined as RNA molecules that do not encode proteins, but recent evidence has proven that peptides/proteins encoded by ncRNAs do indeed exist and usually contain less than 100 amino acids. These peptides/proteins play an important role in regulating tumor energy metabolism, epithelial to mesenchymal transition of cancer cells, the stability of the c-Myc oncoprotein, and the ubiquitination and degradation of proliferating cell nuclear antigen (PCNA). These peptides/proteins represent promising drug targets for fighting against tumor growth or biomarkers for predicting the prognosis of cancer patients.

N-Methyladenine DNA Modification in the Human Genome.

DNA N-methyladenine (6mA) modification is the most prevalent DNA modification in prokaryotes, but whether it exists in human cells and whether it plays a role in human diseases remain enigmatic. Here, we showed that 6mA is extensively present in the human genome, and we cataloged 881,240 6mA sites accounting for ∼0.051% of the total adenines.

ECD promotes gastric cancer metastasis by blocking E3 ligase ZFP91-mediated hnRNP F ubiquitination and degradation.

The human ortholog of the Drosophila ecdysoneless gene (ECD) is required for embryonic development and cell-cycle progression; however, its role in cancer progression and metastasis remains unclear. Here, we found that ECD is frequently overexpressed in gastric cancer (GC), especially in metastatic GC, and is correlated with poor clinical outcomes in GC patients. Silencing ECD inhibited GC migration and invasion in vitro and metastasis in vivo, while ECD overexpression promoted GC migration and invasion.

A Peptide Encoded by a Putative lncRNA HOXB-AS3 Suppresses Colon Cancer Growth.

A substantial fraction of eukaryotic transcripts are considered long non-coding RNAs (lncRNAs), which regulate various hallmarks of cancer. Here, we discovered that the lncRNA HOXB-AS3 encodes a conserved 53-aa peptide. The HOXB-AS3 peptide, not lncRNA, suppresses colon cancer (CRC) growth.

Correlation Between Autophagy and Collagen Deposition in Patients With Pelvic Organ Prolapse.

Objectives: The aim of this study was to explore the link between autophagy and collagen metabolism in patients with pelvic organ prolapse (POP) by detecting the expressions of autophagy factors, collagen, desmin, cytokeratin, and vimentin.

Methods: Histology of anterior vaginal wall and uterosacral ligament was assessed by hematoxylin-eosin staining in POP and non-POP control patients (n = 50 per group). Expressions of collagen types I and III, LC3II, beclin 1, and p62 were examined by Western blot analysis.

POU2F1 over-expression correlates with poor prognoses and promotes cell growth and epithelial-to-mesenchymal transition in hepatocellular carcinoma.

Despite recent efforts to understand activities of POU domain class 2 transcription factor 1 (POU2F1), little is known about the roles of POU2F1 in hepatocellular carcinoma (HCC) tumorigenesis and its correlation with any clinicopathological feature of HCC. In this study, we found that POU2F1 was significantly up-regulated in HCC specimens compared with adjacent non-cancerous liver specimens. The high POU2F1 protein expression level positively correlated with large tumor size, high histological grade, tumor metastasis and advanced clinical stage, and HCC patients with high POU2F1 levels exhibited poor prognoses.

Down-regulation of TRPS1 stimulates epithelial-mesenchymal transition and metastasis through repression of FOXA1.

The tricho-rhino-phalangeal syndrome 1 gene (TRPS1), which was initially found to be associated with tricho-rhino-phalangeal syndrome, is critical for the development and differentiation of bone, hair follicles and kidney. However, its role in cancer progression is largely unknown. In this study, we demonstrated that down-regulation of TRPS1 correlated with distant metastasis, tumour recurrence and poor survival rate in cancer patients.

Amplification of ACK1 promotes gastric tumorigenesis via ECD-dependent p53 ubiquitination degradation.

Amplification or over-expression of an activated Cdc42-associated kinase 1 (ACK1) gene is common in breast, lung and ovarian cancers. However, little is known about the role of ACK1 in gastric tumorigenesis. Here, we found that DNA copy numbers of the ACK1 gene and its mRNA expression levels were significantly increased in gastric cancer (GC) compared to normal gastric tissues.

Epigenetic silencing of ITGA2 by MiR-373 promotes cell migration in breast cancer.

The loss of ITGA2 plays an important role in cancer metastasis in several solid cancers. However, the molecular mechanism of ITGA2 loss in primary cancers remains unclear. In this study, we found that a lower ITGA2 protein level was observed in breast cancers compared to adjacent non-cancerous breast tissues.

iTRAQ protein profile analysis of neuroblastoma (NA) cells infected with the rabies viruses rHep-Flury and Hep-dG.

The rabies virus (RABV) glycoprotein (G) is the principal contributor to the pathogenicity and protective immunity of RABV. In a previous work, we reported that recombinant rabies virus Hep-dG, which was generated by reverse genetics to carry two copies of the G-gene, showed lower virulence than the parental virus rHep-Flury in suckling mice with a better immune protection effect. To better understand the mechanisms underlying rabies virus attenuation and the role of glycoprotein G, isobaric tags for relative and absolute quantitation (iTRAQ) was performed to identify and quantify distinct proteins.

MiR-373 drives the epithelial-to-mesenchymal transition and metastasis via the miR-373-TXNIP-HIF1α-TWIST signaling axis in breast cancer.

Our previous proteomics study revealed that thioredoxin-interacting protein (TXNIP) was down-regulated by miR-373. However, little is known of the mechanism by which miR-373 decreases TXNIP to stimulate metastasis. In this study, we show that miR-373 promotes the epithelial-to-mesenchymal transition (EMT) in breast cancer.