DYRK1A interacts with the tuberous sclerosis complex and promotes mTORC1 activity.

DYRK1A, a ubiquitously expressed kinase is linked to the dominant intellectual developmental disorder, microcephaly, and Down syndrome in humans. It regulates numerous cellular processes such as cell cycle, vesicle trafficking, and microtubule assembly. DYRK1A is a critical regulator of organ growth; however, how it regulates organ growth is not fully understood.

Loss of LOXL2 Promotes Uterine Hypertrophy and Tumor Progression by Enhancing H3K36ac-Dependent Gene Expression.

Unlabelled: Lysyl oxidase-like 2 (LOXL2) is a member of the scavenger receptor cysteine-rich (SRCR) repeat carrying LOX family. Although LOXL2 is suspected to be involved in histone association and chromatin modification, the role of LOXL2 in epigenetic regulation during tumorigenesis and cancer progression remains unclear. Here, we report that nuclear LOXL2 associates with histone H3 and catalyzes H3K36ac deacetylation and deacetylimination.

Synthesis and characterization of arabinoxylan-bis[2-(methacryloyloxy)ethyl] phosphate crosslinked copolymer network by high energy gamma radiation for use in controlled drug delivery applications.

Keeping in view the therapeutic important dietary fiber psyllium, herein this research report its potential has been explored for the formation of sterile hydrogel by high energy radiation induced copolymerization of arabinoxylan-poly bis[2-(methacryloyloxy)ethyl] phosphate (BMEP) for use as drug delivery carrier. The polymeric network structure was characterized by C NMR, FTIR, TGA/DTG and DSC, XRD and AFM techniques. Release profile of a drug cefuroxime and best fit kinetic model were determined.

K63-linked ubiquitination of DYRK1A by TRAF2 alleviates Sprouty 2-mediated degradation of EGFR.

Dual specificity tyrosine phosphorylation regulated kinase 1A, DYRK1A, functions in multiple cellular pathways, including signaling, endocytosis, synaptic transmission, and transcription. Alterations in dosage of DYRK1A leads to defects in neurogenesis, cell growth, and differentiation, and may increase the risk of certain cancers. DYRK1A localizes to a number of subcellular structures including vesicles where it is known to phosphorylate a number of proteins and regulate vesicle biology.

SNP rs17079281 decreases lung cancer risk through creating an YY1-binding site to suppress DCBLD1 expression.

Genome-wide association studies (GWAS) have identified numerous genetic variants that are associated with lung cancer risk, but the biological mechanisms underlying these associations remain largely unknown. Here we investigated the functional relevance of a genetic region in 6q22.2 which was identified to be associated with lung cancer risk in our previous GWAS.

Genome-wide CRISPR screen identifies ELP5 as a determinant of gemcitabine sensitivity in gallbladder cancer.

Gemcitabine is the first-line treatment for locally advanced and metastatic gallbladder cancer (GBC), but poor gemcitabine response is universal. Here, we utilize a genome-wide CRISPR screen to identify that loss of ELP5 reduces the gemcitabine-induced apoptosis in GBC cells in a P53-dependent manner through the Elongator complex and other uridine 34 (U) tRNA-modifying enzymes. Mechanistically, loss of ELP5 impairs the integrity and stability of the Elongator complex to abrogate wobble U tRNA modification, and directly impedes the wobble U modification-dependent translation of hnRNPQ mRNA, a validated P53 internal ribosomal entry site (IRES) trans-acting factor.

PLEK2 promotes gallbladder cancer invasion and metastasis through EGFR/CCL2 pathway.

Background: Gallbladder cancer (GBC) is an extremely malignant tumor with a high mortality rate. Little is known about its invasion and metastasis mechanism so far.

Methods: To identify the driver genes in GBC metastasis, we performed a mRNA microarray of metastatic GBC and paired non-tumor samples, and found PLEK2 was markedly upregulated in GBC tissues.

DYRK1A interacts with histone acetyl transferase p300 and CBP and localizes to enhancers.

DYRK1A, dual-specificity tyrosine phosphorylation-regulated kinase 1A, which is linked to mental retardation and microcephaly, is a member of the CMGC group of kinases. It has both cytoplasmic and nuclear functions, however, molecular mechanisms of how DYRK1A regulates gene expression is not well understood. Here, we identify two histone acetyltransferases, p300 and CBP, as interaction partners of DYRK1A through a proteomics study.

PLZF inhibits proliferation and metastasis of gallbladder cancer by regulating IFIT2.

Gallbladder cancer (GBC) is a malignant cancer with very poor prognosis. Although promyelocytic leukemia zinc-finger protein (PLZF) was reported to be deregulated in numerous cancers and also relevant to clinical prognosis, its role in GBC progression has been little known. In this study, we found PLZF expression was decreased in GBC, correlating to advanced TNM stage, distant metastasis, and shorter overall survival.

miR-92b-3p acts as a tumor suppressor by targeting Gabra3 in pancreatic cancer.

Background: MicroRNAs (miRNAs) can act as oncogenes or tumor suppressors by controlling cell proliferation, differentiation, metastasis and apoptosis, and miRNA dysregulation is involved in the development of pancreatic cancer (PC). Our previous study demonstrated that Gabra3 plays critical roles in cancer progression. However, whether Gabra3 is regulated by miRNAs in PC remains unknown.

MiR-143-5p Deficiency Triggers EMT and Metastasis by Targeting HIF-1α in Gallbladder Cancer.

Background/aims: Early metastasis plays a pivotal role in tumor-caused death in gallbladder cancer (GBC) patients. Increasing evidence suggest that miR-143-5p is an active player involved in cancer metastasis and a potential therapeutic target. However, its role in the development of GBC cells remains unclear.

miR-218-5p restores sensitivity to gemcitabine through PRKCE/MDR1 axis in gallbladder cancer.

Gallbladder cancer (GBC) is one of the most common malignancy of the biliary tract characterized by its high chemoresistant tendency. Although great progresses have been made in recent decades for treating many cancers with anticancer drugs, effective therapeutics methods for anti-GBC are still lacking. Therefore, investigations into identifying the mechanisms underlying the drug resistance of GBC are greatly needed.

An Evolutionary Conserved Epigenetic Mark of Polycomb Response Elements Implemented by Trx/MLL/COMPASS.

Polycomb response elements (PREs) are specific DNA sequences that stably maintain the developmental pattern of gene expression. Drosophila PREs are well characterized, whereas the existence of PREs in mammals remains debated. Accumulating evidence supports a model in which CpG islands recruit Polycomb group (PcG) complexes; however, which subset of CGIs is selected to serve as PREs is unclear.

FXR agonists enhance the sensitivity of biliary tract cancer cells to cisplatin via SHP dependent inhibition of Bcl-xL expression.

Chemoresistance is common in patients with biliary tract cancer (BTC) including gallbladder cancer (GBC) and cholangiocarcinoma (CC). Therefore, it is necessary to identify effective chemotherapeutic agents for BTC. In the present study, we for the first time tested the effect of farnesoid X receptor (FXR) agonists GW4064 and CDCA (chenodeoxycholic acid) in combination with cisplatin (CDDP) on increasing the chemosensitivity in BTC.

Phenylethyl isothiocyanate reverses cisplatin resistance in biliary tract cancer cells via glutathionylation-dependent degradation of Mcl-1.

Biliary tract cancer (BTC) is a highly malignant cancer. BTC exhibits a low response rate to cisplatin (CDDP) treatment, and therefore, an understanding of the mechanism of CDDP resistance is urgently needed. Here, we show that BTC cells develop CDDP resistance due, in part, to upregulation of myeloid cell leukemia 1 (Mcl-1).

Enhancer-associated H3K4 monomethylation by Trithorax-related, the Drosophila homolog of mammalian Mll3/Mll4.

Monomethylation of histone H3 on Lys 4 (H3K4me1) and acetylation of histone H3 on Lys 27 (H3K27ac) are histone modifications that are highly enriched over the body of actively transcribed genes and on enhancers. Although in yeast all H3K4 methylation patterns, including H3K4me1, are implemented by Set1/COMPASS (complex of proteins associated with Set1), there are three classes of COMPASS-like complexes in Drosophila that could carry out H3K4me1 on enhancers: dSet1, Trithorax, and Trithorax-related (Trr). Here, we report that Trr, the Drosophila homolog of the mammalian Mll3/4 COMPASS-like complexes, can function as a major H3K4 monomethyltransferase on enhancers in vivo.

Polycomb repressive complex 2-dependent and -independent functions of Jarid2 in transcriptional regulation in Drosophila.

Jarid2 was recently identified as an important component of the mammalian Polycomb repressive complex 2 (PRC2), where it has a major effect on PRC2 recruitment in mouse embryonic stem cells. Although Jarid2 is conserved in Drosophila, it has not previously been implicated in Polycomb (Pc) regulation. Therefore, we purified Drosophila Jarid2 and its associated proteins and found that Jarid2 associates with all of the known canonical PRC2 components, demonstrating a conserved physical interaction with PRC2 in flies and mammals.

The COMPASS family of H3K4 methylases in Drosophila.

Methylation of histone H3 lysine 4 (H3K4) in Saccharomyces cerevisiae is implemented by Set1/COMPASS, which was originally purified based on the similarity of yeast Set1 to human MLL1 and Drosophila melanogaster Trithorax (Trx). While humans have six COMPASS family members, Drosophila possesses a representative of the three subclasses within COMPASS-like complexes: dSet1 (human SET1A/SET1B), Trx (human MLL1/2), and Trr (human MLL3/4). Here, we report the biochemical purification and molecular characterization of the Drosophila COMPASS family.

Licensed to elongate: a molecular mechanism for MLL-based leukaemogenesis.

The RNA polymerase II (Pol II) elongation factor (ELL) was the first translocation partner of mixed lineage leukaemia (MLL) for which a biochemical function was determined. It was therefore proposed that the regulation of the elongation stage of transcription could be fundamental to MLL-based leukaemogenesis. Recent studies have identified ELL complexed with several of the translocation partners of MLL in a transcriptional super elongation complex (SEC).

Linking H3K79 trimethylation to Wnt signaling through a novel Dot1-containing complex (DotCom).

Epigenetic modifications of chromatin play an important role in the regulation of gene expression. KMT4/Dot1 is a conserved histone methyltransferase capable of methylating chromatin on Lys79 of histone H3 (H3K79). Here we report the identification of a multisubunit Dot1 complex (DotCom), which includes several of the mixed lineage leukemia (MLL) partners in leukemia such as ENL, AF9/MLLT3, AF17/MLLT6, and AF10/MLLT10, as well as the known Wnt pathway modifiers TRRAP, Skp1, and beta-catenin.

The Drosophila insulator proteins CTCF and CP190 link enhancer blocking to body patterning.

Insulator sequences guide the function of distantly located enhancer elements to the appropriate target genes by blocking inappropriate interactions. In Drosophila, five different insulator binding proteins have been identified, Zw5, BEAF-32, GAGA factor, Su(Hw) and dCTCF. Only dCTCF has a known conserved counterpart in vertebrates.

Sternal bands for closure of midline sternotomy leads to better wound healing.

Midline sternotomy is the most common incision for cardiac surgery, but problems of wound healing and sternal instability are still matters of concern. The use of stainless steel wires only was compared with the use of wires plus sternal bands for closure of midline sternotomy wounds in a 2-year period. Of 370 patients in whom only stainless steel wires were used, 14 (3.