Promoting role of pentraxin-3 in esophageal squamous cell carcinoma.

Pentraxin 3 (PTX3) is an inflammatory molecule that is closely related to the proliferation, invasion, and metastasis of cancer. In order to explore the role of PTX3 in the occurrence and development of esophageal carcinoma (ESCA), we modified the PTX3 gene in ESCA cell lines to obtain the model of gene knockout and overexpression and studied cell proliferation, cycle, apoptosis, migration ability, energy metabolism, and sensitivity to chemotherapy and radiotherapy. We observed the increase in cell proliferation, cycle, apoptosis, migration ability, and sensitivity to chemotherapy and radiotherapy in the PTX3 knockout model, while in the PTX3 overexpression model, these phenomena were significantly reduced.

Abrogation of USP7 is an alternative strategy to downregulate PD-L1 and sensitize gastric cancer cells to T cells killing.

Targeting immune checkpoints such as programmed cell death protein 1 (PD-1) and programmed death ligand-1 (PD-L1) have been approved for treating melanoma, gastric cancer (GC) and bladder cancer with clinical benefit. Nevertheless, many patients failed to respond to anti-PD-1/PD-L1 treatment, so it is necessary to seek an alternative strategy for traditional PD-1/PD-L1 targeting immunotherapy. Here with the data from The Cancer Genome Atlas (TCGA) and our in-house tissue library, PD-L1 expression was found to be positively correlated with the expression of ubiquitin-specific processing protease 7 (USP7) in GC.

Correction: Potent and specific MTH1 inhibitors targeting gastric cancer.

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

Oncogenic Role of Guanylate Binding Protein 1 in Human Prostate Cancer.

The Guanylate binding proteins (GBPs) are a family of large GTPases and the most studied GBP family member is the guanylate binding protein 1 (GBP1). Earlier studies revealed that GBP1 expression was inflammatory cytokines-inducible, and most of the studies focused on inflammation diseases. Increasing number of cancer studies began to reveal its biological role in cancers recently, although with contradictory findings in literature.

Gene Knockout In Human Esophageal Squamous Cancer Cells Resulted In Greater Warburg Effect And Aggressive Features In Vitro And In Vivo.

Background: One of the remarkable metabolic characteristics of cancer cells is that they prefer glycolysis rather than oxidative phosphorylation (OXPHOS). Pyruvate dehydrogenase E1 alpha subunit (PDHA1) is an important prerequisite for OXPHOS. Our previous studies have shown that low level of PDHA1 protein expression in esophageal squamous cell cancer (ESCC) was correlated with poor prognosis.

High level of lncRNA H19 expression is associated with shorter survival in esophageal squamous cell cancer patients.

Aim: Long non-coding RNA (lncRNA) is currently considered to play an important regulatory role in various diseases, including tumors, at present a hot topic in research. As a non-coding transcription product of imprinted gene, LncRNA H19 is expressed as a parent imprinted maternal allele without protein-coding ability. Increasing evidence indicates that LncH19 may be a new tumor marker for early clinical diagnosis and prognosis judgment.

Potent and specific MTH1 inhibitors targeting gastric cancer.

Human mutT homolog 1(MTH1), the oxidized dNTP pool sanitizer enzyme, has been reported to be highly expressed in various malignant tumors. However, the oncogenic role of MTH1 in gastric cancer remains to be determined. In the current study, we found that MTH1 was overexpressed in human gastric cancer tissues and cells.

Potent 5-Cyano-6-phenyl-pyrimidin-Based Derivatives Targeting DCN1-UBE2M Interaction.

Neddylation of the Cullin-RING E3 ligases (CRLs) regulates the homeostasis of approximately 20% of cellular proteins. Defective in cullin neddylation 1 (DCN1), as a co-E3 ligase, interacts with UBE2M to enhance the activation of CRLs, and this interaction is emerging as a therapeutic target for human diseases. Here, we present a series of pyrimidin-based small molecular inhibitors targeting DCN1-UBE2M interaction.

USP7: Novel Drug Target in Cancer Therapy.

Ubiquitin specific protease 7 (USP7) is one of the deubiquitinating enzymes (DUB) that erases ubiquitin and protects substrate protein from degradation. Full activity of USP7 requires the C-terminal Ub-like domains fold back onto the catalytic domain, allowing the remodeling of the active site to a catalytically competent state by the C-terminal peptide. Until now, numerous proteins have been identified as substrates of USP7, which play a key role in cell cycle, DNA repair, chromatin remodeling, and epigenetic regulation.

Author Correction: PBX3 is targeted by multiple miRNAs and is essential for liver tumour-initiating cells.

This Article contains an error in Figure 3. In panel g, images representing miR-222-TuD and miR-424-TuD were both taken from the miR-222-TuD image. The correct version of Figure 3 is shown in the accompanying Author Correction.

Anti-senescence role of heterozygous fumarate hydratase gene knockout in rat lung fibroblasts .

Abnormalities in tricarboxylic acid (TCA) cycle function were related to a variety of pathological processes. Fumarate hydratase (FH) is a required enzyme in the TCA cycle. To explore the general influence of FH knockout, we isolated FH rat and normal rat lung fibroblasts and cultured these cells .

Identification of an early diagnostic biomarker of lung adenocarcinoma based on co-expression similarity and construction of a diagnostic model.

Background: The purpose of this study was to achieve early and accurate diagnosis of lung cancer and long-term monitoring of the therapeutic response.

Methods: We downloaded GSE20189 from GEO database as analysis data. We also downloaded human lung adenocarcinoma RNA-seq transcriptome expression data from the TCGA database as validation data.

High SRPX2 protein expression predicts unfavorable clinical outcome in patients with prostate cancer.

Background: Sushi repeat-containing protein X-linked 2 (SRPX2) is overexpressed in a variety of different tumor tissues and correlated with poor prognosis in patients. Little research focuses on the role of SRPX2 expression in prostate cancer (PCa), and the clinicopathological significance of the protein expression in this tumor is relatively unknown. However, our previous transcriptome data from those cancer stem-like cells indicated the role of SRPX2 in PCa.

A Diaper Pad for Diaper-Based Urine Collection and Colorimetric Screening of Urinary Biomarkers.

The high prevalence of urinary tract infection in aging adults is a challenging aspect of geriatric care. Incontinence and cognitive/functional impairment make collection of urine samples difficult and often require either catheterization for sample collection, which is a risk factor for infections, or more lenient criteria for initiating antibiotic treatment. We report the development of a diaper inlay with absorbent materials, superabsorbent polymer-based valve and chemical reaction pads for rapid screening of urinary tract infection of incontinent diaper-wearing elderly receivers of home care services.

MtDNA depletion influences the transition of CD44 subtypes in human prostate cancer DU145 cells.

Our earlier study revealed that long-term ethidium bromide application causes mitochondrial DNA depletion in human prostate cancer DU145 cell line (DU145), and this DU145 subline appears to have expanded CD44 cell population than its parental wild type DU145 cells (DU145). Increasing evidence suggests that CD44 cells are highly cancer stem cell like, but it is not clear about their dynamic transition between CD44 and CD44 phenotypes in prostate cancer cells, and how it is affected by mitochondrial DNA depletion. To address these questions, four cell subpopulations were isolated from both DU145 and DU145 cell lines based on their CD44 expression level and mitochondrial membrane potential.

Metabolic reprogramming is associated with flavopiridol resistance in prostate cancer DU145 cells.

Flavopiridol (FP) is a pan-cyclin dependent kinase inhibitor, which shows strong efficacy in inducing cancer cell apoptosis. Although FP is potent against most cancer cells in vitro, unfortunately it proved less efficacious in clinical trials in various aggressive cancers. To date, the molecular mechanisms of the FP resistance are mostly unknown.

Mitochondrial pyruvate carrier function determines cell stemness and metabolic reprogramming in cancer cells.

One of the remarkable features of cancer cells is aerobic glycolysis, a phenomenon known as the "Warburg Effect", in which cells rely preferentially on glycolysis instead of oxidative phosphorylation (OXPHOS) as the main energy source even in the presence of high oxygen tension. Cells with dysfunctional mitochondria are unable to generate sufficient ATP from mitochondrial OXPHOS, and then are forced to rely on glycolysis for ATP generation. Here we report our results in a prostate cancer cell line in which the mitochondrial pyruvate carrier 1 (MPC1) gene was knockout.

AQP4 Association with Amyloid Deposition and Astrocyte Pathology in the Tg-ArcSwe Mouse Model of Alzheimer's Disease.

Amyloid-β deposition in senile plaques is one of the main pathological changes in Alzheimer's disease (AD). We previously reported that aquaporin-4 (AQP4) is redistributed within the astrocytes in cerebral amyloid angiopathy in the tg-ArcSwe mouse model of AD, suggesting that AQP4 may participate in amyloid-β deposition. However, the role of AQP4 in plaque formation is not currently clear.

Pyruvate dehydrogenase expression is negatively associated with cell stemness and worse clinical outcome in prostate cancers.

Cells generate adenosine-5'-triphosphate (ATP), the major currency for energy-consuming reactions, through mitochondrial oxidative phosphorylation (OXPHOS) and glycolysis. One of the remarkable features of cancer cells is aerobic glycolysis, also known as the "Warburg Effect", in which cancer cells rely preferentially on glycolysis instead of mitochondrial OXPHOS as the main energy source even in the presence of high oxygen tension. One of the main players in controlling OXPHOS is the mitochondrial gatekeeperpyruvate dehydrogenase complex (PDHc) and its major subunit is E1α (PDHA1).

Mitochondrial pyruvate carrier function is negatively linked to Warburg phenotype in vitro and malignant features in esophageal squamous cell carcinomas.

Aerobic glycolysis is one of the emerging hallmarks of cancer cells. In this study, we investigated the relationship between blocking mitochondrial pyruvate carrier (MPC) with MPC blocker UK5099 and the metabolic alteration as well as aggressive features of esophageal squamous carcinoma. It was found that blocking pyruvate transportation into mitochondria attenuated mitochondrial oxidative phosphorylation (OXPHOS) and triggered aerobic glycolysis, a feature of Warburg effect.