CYR61 Acts as an Intracellular Microtubule-Associated Protein and Coordinates Mitotic Progression via PLK1-FBW7 Pathway.

Cysteine-rich angiogenic inducer 61 (CYR61), also called CCN1, has long been characterized as a secretory protein. Nevertheless, the intracellular function of CYR61 remains unclear. Here, we found that CYR61 is important for proper cell cycle progression.

RNA-binding protein MEX3A controls G1/S transition via regulating the RB/E2F pathway in clear cell renal cell carcinoma.

MEX3A is an RNA-binding protein that mediates mRNA decay through binding to 3' untranslated regions. However, its role and mechanism in clear cell renal cell carcinoma remain unknown. In this study, we found that expression was transcriptionally activated by ETS1 and upregulated in clear cell renal cell carcinoma.

Activation of bivalent factor DLX5 cooperates with master regulator TP63 to promote squamous cell carcinoma.

To reconstruct systematically hyperactive transcription factor (TF)-dependent transcription networks in squamous cell carcinomas (SCCs), a computational method (ELMER) was applied to 1293 pan-SCC patient samples, and 44 hyperactive SCC TFs were identified. As a top candidate, DLX5 exhibits a notable bifurcate re-configuration of its bivalent promoter in cancer. Specifically, DLX5 maintains a bivalent state in normal tissues; its promoter is hypermethylation, leading to DLX5 transcriptional silencing in esophageal adenocarcinoma (EAC).

SMYD3 promotes hepatocellular carcinoma progression by methylating S1PR1 promoters.

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. SET and MYND domain-containing protein 3 (SMYD3) has been shown to promote the progression of various types of human cancers, including liver cancer; however, the detailed molecular mechanism is still largely unknown. Here, we report that SMYD3 expression in HCC is an independent prognostic factor for survival and promotes the proliferation and migration of HCC cells.

Aberrant DNA Methylation in Esophageal Squamous Cell Carcinoma: Biological and Clinical Implications.

Almost all cancer cells possess multiple epigenetic abnormalities, which cooperate with genetic alterations to enable the acquisition of cancer hallmarks during tumorigenesis. As the most frequently found epigenetic change in human cancers, aberrant DNA methylation manifests at two major forms: global genomic DNA hypomethylation and locus-specific promoter region hypermethylation. It has been recognized as a critical contributor to esophageal squamous cell carcinoma (ESCC) malignant transformation.

CEBPG promotes esophageal squamous cell carcinoma progression by enhancing PI3K-AKT signaling.

CCAAT/enhancer binding proteins (CEBPs, including CEBPA, CEBPB, CEBPD, CEBPE, CEBPG, and CEBPZ) play critical roles in a variety of physiological and pathological processes. However, the molecular characteristics and biological significance of CEBPs in esophageal squamous cell carcinoma (ESCC) have rarely been reported. Here, we show that most of the CEBPs are upregulated and accompanied with copy number amplifications in ESCC.

ATM-Dependent Recruitment of BRD7 is required for Transcriptional Repression and DNA Repair at DNA Breaks Flanking Transcriptional Active Regions.

Repair of DNA double-strand breaks (DSBs) is essential for genome integrity, and is accompanied by transcriptional repression at the DSB regions. However, the mechanisms how DNA repair induces transcriptional inhibition remain elusive. Here, it is identified that BRD7 participates in DNA damage response (DDR) and is recruited to the damaged chromatin via ATM signaling.

LncRNA DSCAM-AS1 interacts with YBX1 to promote cancer progression by forming a positive feedback loop that activates FOXA1 transcription network.

The forkhead box A1 (FOXA1) is a crucial transcription factor in initiation and development of breast, lung and prostate cancer. Previous studies about the FOXA1 transcriptional network were mainly focused on protein-coding genes. Its regulatory network of long non-coding RNAs (lncRNAs) and their role in FOXA1 oncogenic activity remains unknown.

Pyruvate Kinase M2 Tetramerization Protects against Hepatic Stellate Cell Activation and Liver Fibrosis.

Liver fibrosis is an increasing health problem worldwide, for which no effective antifibrosis drugs are available. Although the involvement of aerobic glycolysis in hepatic stellate cell (HSC) activation has been reported, the role of pyruvate kinase M2 (PKM2) in liver fibrogenesis still remains unknown. We examined PKM2 expression and location in liver tissues and primary hepatic cells.

Biological Significance of Tumor Heterogeneity in Esophageal Squamous Cell Carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a common and aggressive malignancy, with hitherto dismal clinical outcome. Genomic analyses of patient samples reveal a complex heterogeneous landscape for ESCC, which presents in both intertumor and intratumor forms, manifests at both genomic and epigenomic levels, and contributes significantly to tumor evolution, drug resistance, and metastasis. Here, we review the important molecular characteristics underlying ESCC heterogeneity, with an emphasis on genomic aberrations and their functional contribution to cancer evolutionary trajectories.

Macrophage-derived exosomal microRNA-501-3p promotes progression of pancreatic ductal adenocarcinoma through the TGFBR3-mediated TGF-β signaling pathway.

Background: Exosomes from cancer cells or immune cells, carrying bio-macromolecules or microRNAs (miRNAs), participate in tumor pathogenesis and progression by modulating microenvironment. Our study aims to investigate the role of these microRNA-501-3p (miR-501-3p) containing exosomes derived from tumor-associated macrophage (TAM) in the progression of pancreatic ductal adenocarcinoma (PDAC).

Methods: Firstly, the function of TAM recruitment in PDAC tissues was assessed, followed by identification of the effects of M2 macrophage-derived exosomes on PDAC cell activities and tumor formation and metastasis in mice.

Poly(ADP-ribosyl)ation of BRD7 by PARP1 confers resistance to DNA-damaging chemotherapeutic agents.

The bromodomain-containing protein 7 (BRD7) is a tumour suppressor protein with critical roles in cell cycle transition and transcriptional regulation. Whether BRD7 is regulated by post-translational modifications remains poorly understood. Here, we find that chemotherapy-induced DNA damage leads to the rapid degradation of BRD7 in various cancer cell lines.

Super-enhancer-associated MEIS1 promotes transcriptional dysregulation in Ewing sarcoma in co-operation with EWS-FLI1.

As the second most common malignant bone tumor in children and adolescents, Ewing sarcoma is initiated and exacerbated by a chimeric oncoprotein, most commonly, EWS-FLI1. In this study, we apply epigenomic analysis to characterize the transcription dysregulation in this cancer, focusing on the investigation of super-enhancer and its associated transcriptional regulatory mechanisms. We demonstrate that super-enhancer-associated transcripts are significantly enriched in EWS-FLI1 target genes, contribute to the aberrant transcriptional network of the disease, and mediate the exceptional sensitivity of Ewing sarcoma to transcriptional inhibition.

ARID1A and CEBPα cooperatively inhibit UCA1 transcription in breast cancer.

As one of the primary members of SWI/SNF chromatin remodeling complexes, ARID1A contains frequent loss-of-function mutations in many types of cancers. However, the molecular mechanisms underlying ARID1A deficiency in cancer biology remain to be investigated. Using breast cancer as a model, we report that silencing ARID1A significantly increased cellular proliferation and migration.

Super-Enhancer-Driven Long Non-Coding RNA LINC01503, Regulated by TP63, Is Over-Expressed and Oncogenic in Squamous Cell Carcinoma.

Background & Aims: Long non-coding RNAs (lncRNAs) are expressed in tissue-specific pattern, but it is not clear how these are regulated. We aimed to identify squamous cell carcinoma (SCC)-specific lncRNAs and investigate mechanisms that control their expression and function.

Methods: We studied expression patterns and functions of 4 SCC-specific lncRNAs.

Genomic and Epigenomic Heterogeneity of Hepatocellular Carcinoma.

Understanding the intratumoral heterogeneity of hepatocellular carcinoma is instructive for developing personalized therapy and identifying molecular biomarkers. Here we applied whole-exome sequencing to 69 samples from 11 patients to resolve the genetic architecture of subclonal diversification. Spatial genomic diversity was found in all 11 hepatocellular carcinoma cases, with 29% of driver mutations being heterogeneous, including TERT, ARID1A, NOTCH2, and STAG2.

Expression of CCN family members correlates with the clinical features of hepatocellular carcinoma.

Studies have reported that the CCN family of proteins plays an important role in stimulating tumorigenesis. However, the relationship between the CCN protein family members and the features of hepatocellular carcinoma (HCC) remains unclear. The objective of this study was to determine the relationship between the expression levels of CCN protein family members and the features of HCC.

Dual targeting of glioblastoma multiforme with a proteasome inhibitor (Velcade) and a phosphatidylinositol 3-kinase inhibitor (ZSTK474).

Proteasome inhibitors have been proven to be effective anticancer compounds in many tumor models, including glioblastoma multiforme (GBM). In this study, we found that the proteasome inhibitor Velcade (PS-341/bortezomib) caused GBM cell death while simultaneously activating the PI3K/Akt pathway. Therefore, we sought to investigate if the PI3K inhibitor ZSTK474 would enhance the effectiveness of Velcade in anticancer therapy.