Organ defects of the Usp7 mutant mouse strain indicate the essential role of K63-polyubiquitinated Usp7 in organ formation.

Background: K63-linked polyubiquitination of proteins have nonproteolytic functions and regulate the activity of many signal transduction pathways. USP7, a HIF1α deubiquitinase, undergoes K63-linked polyubiquitination under hypoxia. K63-polyubiquitinated USP7 serves as a scaffold to anchor HIF1α, CREBBP, the mediator complex, and the super elongation complex to enhance HIF1α-induced gene transcription.

Nafamostat mesylate overcomes endocrine resistance of breast cancer through epigenetic regulation of CDK4 and CDK6 expression.

Breast cancer is common worldwide, and the estrogen receptor-positive subtype accounts for approximately 70% of breast cancer in women. Tamoxifen and fulvestrant are drugs currently used for endocrinal therapy. Breast cancer exhibiting endocrine resistance can undergo metastasis and lead to the death of breast cancer patients.

Chromatin accessibility analysis identifies GSTM1 as a prognostic marker in human glioblastoma patients.

Background: Glioblastoma (GBM) is a malignant human brain tumor that has an extremely poor prognosis. Classic mutations such as IDH (isocitrate dehydrogenase) mutations, EGFR (epidermal growth factor receptor) alternations, and MGMT (O6-methylguanine-methyltransferase) promoter hypermethylation have been used to stratify patients and provide prognostic significance. Epigenetic perturbations have been demonstrated in glioblastoma tumorigenesis.

The role of hypoxia-induced long noncoding RNAs (lncRNAs) in tumorigenesis and metastasis.

Long noncoding RNAs (lncRNAs) are noncoding RNAs with length greater than 200 nt. The biological roles and mechanisms mediated by lncRNAs have been extensively investigated. Hypoxia is a proven microenvironmental factor that promotes solid tumor metastasis.

USP7 facilitates SMAD3 autoregulation to repress cancer progression in p53-deficient lung cancer.

USP7, one of the most abundant ubiquitin-specific proteases (USP), plays multifaceted roles in many cellular events, including oncogenic pathways. Accumulated studies have suggested that USP7, through modulating the MDM2/MDMX-p53 pathway, is a promising target for cancer treatment; however, little is known about the function of USP7 in p53-deficient tumors. Here we report that USP7 regulates the autoregulation of SMAD3, a key regulator of transforming growth factor β (TGFβ) signaling, that represses the cell progression of p53-deficient lung cancer.

Liquid-liquid phase separation (LLPS) in cellular physiology and tumor biology.

Liquid-liquid phase separation (LLPS) has emerged as a mechanism that has been used to explain the formation of known organelles (e.g. nucleoli, promyelocytic leukemia nuclear bodies (PML NBs), etc) as well as other membraneless condensates (e.

Induction of epithelial-mesenchymal transition (EMT) by hypoxia-induced lncRNA through regulating the histone 4 lysine 16 acetylation (H4K16Ac) mark.

Hypoxia activates various long noncoding RNAs (lncRNAs) to induce the epithelial-mesenchymal transition (EMT) and tumor metastasis. The hypoxia/HIF-1α-regulated lncRNAs that also regulate a specific histone mark and promote EMT and metastasis have not been identified. We performed RNA-sequencing dataset analysis to search for such lncRNAs and lncRNA was the hypoxia-induced lncRNA with the highest hazard ratio.

Clinical predictors for biochemical failure in patients with positive surgical margin after robotic-assisted radical prostatectomy.

Objective: Patients with positive surgical margins (PSMs) after radical prostatectomy for localized prostate cancer have a higher risk of biochemical failure (BCF). We investigated the risk factors of BCF in patients with PSMs after robotic-assisted radical prostatectomy (RARP).

Methods: We evaluated 462 patients who underwent RARP in a single medical center from 2006 through 2013.

Identification and validation of a miRNA-based prognostic signature for cervical cancer through an integrated bioinformatics approach.

Cervical cancer is the fourth most common cancer in women worldwide. Increasing evidence has shown that miRNAs are related to the progression of cervical cancer. However, the mechanisms that affect the prognosis of cancer are still largely unknown.

Targeting interleukin-17 receptor B enhances gemcitabine sensitivity through downregulation of mucins in pancreatic cancer.

Pancreatic cancer is the fourth leading cause of death worldwide due to its poorest prognoses with a 7% 5-year survival rate. Eighty percent of pancreatic cancer patients relapse after chemotherapy and develop early metastasis and drug resistance. Resistance to nucleoside analog gemcitabine frequently used in first-line therapy is an urgent issue in pancreatic cancer treatment.

Omics-Based Platforms: Current Status and Potential Use for Cholangiocarcinoma.

Cholangiocarcinoma (CCA) has been identified as a highly malignant cancer that can be transformed from epithelial cells of the bile duct, including intrahepatic, perihilar and extrahepatic. High-resolution imaging tools (abdominal ultrasound, computed tomography and percutaneous transhepatic cholangial drainage) are recruited for diagnosis. However, the lack of early diagnostic biomarkers and treatment evaluation can lead to serious outcomes and poor prognosis (i.

The epigenetic roles of DNA N-Methyladenine (6mA) modification in eukaryotes.

The DNA N-methyladenine (6mA) modification is a prevalent epigenetic mark in prokaryotes, but the low abundance of 6mA in eukaryotes has recently received attention. The possible role of 6mA as an epigenetic mark in eukaryotes is starting to be recognized. This review article addresses the epigenetic roles of 6mA in eukaryotes.

The role of miRNA biogenesis and DDX17 in tumorigenesis and cancer stemness.

Cancer stemness represents one of the major mechanisms that predispose patients to tumor aggressiveness, metastasis, and treatment resistance. MicroRNA biogenesis is an important process controlling miRNA processing and maturation. Deregulation of miRNA biogenesis can lead to tumorigenesis and cancer stemness.

Hypoxia-induced lncRNA RP11-390F4.3 promotes epithelial-mesenchymal transition (EMT) and metastasis through upregulating EMT regulators.

Hypoxia-induced long noncoding RNAs (lncRNAs) have been shown to induce tumor metastasis. However, lncRNAs that are regulated by hypoxia/HIF-1α and subsequently control the expression of multiple epithelial-mesenchymal transition (EMT) regulators have not been identified. To identify such lncRNAs, analysis of RNA-sequencing datasets was performed.

Lactotransferrin Downregulation Drives the Metastatic Progression in Clear Cell Renal Cell Carcinoma.

Clear cell renal cell carcinoma (ccRCC) is the main type of RCC, which is the most common type of malignant kidney tumor in adults. A subpopulation (>30%) of ccRCC patients develop metastasis; however, the molecular mechanism remains largely unknown. Here, we found that LTF, the gene encoding lactotransferrin, is dramatically downregulated in primary tumors compared to normal tissues derived from ccRCC patients deposited in The Cancer Genome Atlas (TCGA) database and is a favorable prognostic marker.

N-Deoxyadenosine Methylation in Mammalian Mitochondrial DNA.

N-Methyldeoxyadenosine (6mA) has recently been shown to exist and play regulatory roles in eukaryotic genomic DNA (gDNA). However, the biological functions of 6mA in mammals have yet to be adequately explored, largely due to its low abundance in most mammalian genomes. Here, we report that mammalian mitochondrial DNA (mtDNA) is enriched for 6mA.

Epigenetic regulation of epithelial-mesenchymal transition: focusing on hypoxia and TGF-β signaling.

Epithelial-mesenchymal transition (EMT) is an important process triggered during cancer metastasis. Regulation of EMT is mostly initiated by outside signalling, including TGF-β, growth factors, Notch ligand, Wnt, and hypoxia. Many signalling pathways have been delineated to explain the molecular mechanisms of EMT.

Identification of new hypoxia-regulated epithelial-mesenchymal transition marker genes labeled by H3K4 acetylation.

Hypoxia-induced epithelial-mesenchymal transition (EMT) involves the interplay between chromatin modifiers histone deacetylase 3 (HDAC3) and WDR5. The histone mark histone 3 lysine 4 acetylation (H3K4Ac) is observed in the promoter regions of various EMT marker genes (eg, CDH1 and VIM). To further define the genome-wide location of H3K4Ac, a chromatin immunoprecipitation followed by massively parallel DNA sequencing (ChIP-seq) analysis was performed using a head and neck squamous cell carcinoma (HNSCC) FaDu cell line under normoxia and hypoxia.

Regulation of miRNA Biogenesis and Histone Modification by K63-Polyubiquitinated DDX17 Controls Cancer Stem-like Features.

Markers of cancer stemness predispose patients to tumor aggressiveness, drug and immunotherapy resistance, relapse, and metastasis. DDX17 is a cofactor of the Drosha-DGCR8 complex in miRNA biogenesis and transcriptional coactivator and has been associated with cancer stem-like properties. However, the precise mechanism by which DDX17 controls cancer stem-like features remains elusive.

Endothelial progenitor cells control the angiogenic switch in mouse lung metastasis.

Angiogenesis-mediated progression of micrometastasis to lethal macrometastasis is the major cause of death in cancer patients. Here, using mouse models of pulmonary metastasis, we identify bone marrow (BM)-derived endothelial progenitor cells (EPCs) as critical regulators of this angiogenic switch. We show that tumors induce expression of the transcription factor Id1 in the EPCs and that suppression of Id1 after metastatic colonization blocked EPC mobilization, caused angiogenesis inhibition, impaired pulmonary macrometastases, and increased survival of tumor-bearing animals.

Bone marrow-derived endothelial progenitor cells are a major determinant of nascent tumor neovascularization.

Tumors build vessels by cooption of pre-existing vasculature and de novo recruitment of bone marrow (BM)-derived endothelial progenitor cells (EPCs). However, the contribution and the functional role of EPCs in tumor neoangiogenesis are controversial. Therefore, by using genetically marked BM progenitor cells, we demonstrate the precise spatial and temporal contribution of EPCs to the neovascularization of three transplanted and one spontaneous breast tumor in vivo using high-resolution microscopy and flow cytometry.

Genomics and proteomics approaches in understanding tumor angiogenesis.

Functional genomic and proteomic approaches have begun to revolutionize cancer research. The advent of powerful technologies, such as DNA microarrays, serial analysis of gene expression, RNA interference and proteomics, has accelerated investigations of gene identification and function at a scale never before accomplished. Approaches integrating these technologies with high-throughput forward and reverse genetic screens, are already providing insights into the mechanistic understanding of angiogenesis, leading to the identification of proteins that can be used for selective targeting of tumor vessels.