Aberrant accumulation of Kras-dependent pervasive transcripts during tumor progression renders cancer cells dependent on PAF1 expression.

KRAS is the most commonly mutated oncogene in human cancer, and mutant KRAS is responsible for over 90% of pancreatic ductal adenocarcinoma (PDAC), the most lethal cancer. Here, we show that RNA polymerase II-associated factor 1 complex (PAF1C) is specifically required for survival of PDAC but not normal adult pancreatic cells. We show that PAF1C maintains cancer cell genomic stability by restraining overaccumulation of enhancer RNAs (eRNAs) and promoter upstream transcripts (PROMPTs) driven by mutant Kras.

Carma3 Protects from Liver Injury by Preserving Mitochondrial Integrity in Liver Sinusoidal Endothelial Cells.

Carma3 is an intracellular scaffolding protein that can form complex with Bcl10 and Malt1 to mediate G protein-coupled receptor- or growth factor receptor-induced NF-κB activation. However, the in vivo function of Carma3 has remained elusive. Here, by establishing a Con A-induced autoimmune hepatitis model, we show that liver injury is exacerbated in mice.

Mutant Kras co-opts a proto-oncogenic enhancer network in inflammation-induced metaplastic progenitor cells to initiate pancreatic cancer.

Kras-activating mutations display the highest incidence in pancreatic ductal adenocarcinoma. Pancreatic inflammation accelerates mutant Kras-driven tumorigenesis in mice, suggesting high selectivity in the cells that oncogenic Kras transforms, although the mechanisms dictating this specificity are poorly understood. Here we show that pancreatic inflammation is coupled to the emergence of a transient progenitor cell population that is readily transformed in the presence of mutant KrasG12D.

Antibodies and vaccines against Middle East respiratory syndrome coronavirus.

The Middle East respiratory syndrome coronavirus (MERS-CoV) has spread through 27 countries and infected more than 2,200 people since its first outbreak in Saudi Arabia in 2012. The high fatality rate (35.4%) of this novel coronavirus and its persistent wide spread infectiousness in animal reservoirs have generated tremendous global public health concern.

Expression of the hormonal FGF co-receptor Klotho beta in the Xenopus laevis model.

Klotho beta (Klb), a single-pass transmembrane protein, has been described as a co-receptor for endocrine FGFs, such as FGF15/19 and FGF21, to regulate critical metabolic processes in multiple organs and tissues in adult mice. However, its function during early embryonic development remains largely unknown. In this paper, we evaluated for the first time the expression of klb mRNA during early development of Xenopus laevis by RT-PCR and whole mount in situ hybridization.

Compound C induces protective autophagy in human cholangiocarcinoma cells via Akt/mTOR-independent pathway.

Compound C, a well-known inhibitor of AMP-activated protein kinase (AMPK), has been reported to exert antitumor activities in some types of cells. Whether compound C can exert antitumor effects in human cholangiocarcinoma (CCA) remains unknown. Here, we demonstrated that compound C is a potent inducer of cell death and autophagy in human CCA cells.

KDM3A-mediated demethylation of histone H3 lysine 9 facilitates the chromatin binding of Neurog2 during neurogenesis.

Neurog2 is a crucial regulator of neuronal fate specification and differentiation and However, it remains unclear how Neurog2 transactivates neuronal genes that are silenced by repressive chromatin. Here, we provide evidence that the histone H3 lysine 9 demethylase KDM3A facilitates the Neurog2 (formerly known as Xngnr1) chromatin accessibility during neuronal transcription. Loss-of-function analyses reveal that KDM3A is not required for the transition of naive ectoderm to neural progenitor cells but is essential for primary neuron formation.

Epigenetic regulation of left-right asymmetry by DNA methylation.

DNA methylation is a major epigenetic modification; however, the precise role of DNA methylation in vertebrate development is still not fully understood. Here, we show that DNA methylation is essential for the establishment of the left-right (LR) asymmetric body plan during vertebrate embryogenesis. Perturbation of DNA methylation by depletion of () or in zebrafish embryos leads to defects in dorsal forerunner cell (DFC) specification or collective migration, laterality organ malformation, and disruption of LR patterning.

c‑Myc promotes cholangiocarcinoma cells to overcome contact inhibition via the mTOR pathway.

The loss of contact inhibition is a hallmark of a wide range of human cancer cells. Yet, the precise mechanism behind this process is not fully understood. c‑Myc plays a pivotal role in carcinogenesis, but its involvement in regulating contact inhibition has not been explored to date.

The RNF146 E3 ubiquitin ligase is required for the control of Wnt signaling and body pattern formation in Xenopus.

The RING finger protein Rnf146 encodes an E3 ubiquitin ligase capable of targeting poly-ADP-ribosylated substrates for proteasomal degradation. Rnf146 has been identified as a critical regulator of Axin1 and thus of Wnt/β-catenin signaling. However its physiological significance in vertebrate embryonic development remains to be demonstrated.

Ascl1 represses the mesendoderm induction in Xenopus.

Ascl1 is a multi-functional regulator of neural development in invertebrates and vertebrates. Ectopic expression of Ascl1 can generate functional neurons from non-neural somatic cells. The abnormal expression of ASCL1 has been reported in several types of carcinomas.

The MLL/Setd1b methyltransferase is required for the Spemann's organizer gene activation in Xenopus.

Wdr5 is an essential component of SET/MLL methylase complexes that catalyze histone H3 lysine 4 trimethylation. The maternal Wnt/β-catenin signaling is necessary for the H3K4me3 deposition at organizer genes in early Xenopus embryos. However, it remains unknown whether any component of SET/MLL methylase complex is required for Wnt signaling to establish H3K4me3 at its targets during the organizer induction.

A novel role for Ascl1 in the regulation of mesendoderm formation via HDAC-dependent antagonism of VegT.

Maternally expressed proteins function in vertebrates to establish the major body axes of the embryo and to establish a pre-pattern that sets the stage for later-acting zygotic signals. This pre-patterning drives the propensity of Xenopus animal cap cells to adopt neural fates under various experimental conditions. Previous studies found that the maternally expressed transcription factor, encoded by the Xenopus achaete scute-like gene ascl1, is enriched at the animal pole.

NF2/Merlin is required for the axial pattern formation in the Xenopus laevis embryo.

The NF2 gene product Merlin is a FERM-domain protein possessing a broad tumor-suppressing function. NF2/Merlin has been implicated in regulating multiple signaling pathways critical for cell growth and survival. However, it remains unknown whether NF2/Merlin regulates Wnt/β-catenin signaling during vertebrate embryogenesis.

Sebox regulates mesoderm formation in early amphibian embryos.

Background: Mix/Bix genes are important regulators of mesendoderm formation during vertebrate embryogenesis. Sebox, an additional member of this gene family, has been implicated in endoderm formation during early embryogenesis in zebrafish. However, it remains unclear whether Sebox plays a unique role in early Xenopus embryos.