LAMC2, as a unique chain in the Laminin 5 molecule, has been found to be associated with malignant metastases in some cancers. However, the roles and mechanisms by which LAMC2 affects the migration and invasion of pancreatic cancer cells remain unclear. First, we found that laminin 5/LAMC2 and its receptors were highly expressed in pancreatic cancer tissues and cells. Then, we investigated the effects

Centromeres are essential components of all eukaryotic chromosomes, including artificial/synthetic ones built in the laboratory. In humans, centromeres are typically located on repetitive α-satellite DNA, and these sequences are the “major ingredient” in first-generation human artificial chromosomes (HACs). Repetitive centromeric sequences present a major challenge for the design of synthetic mammalian

Tumor-associated macrophages (TAMs) and their M2-type extremely promote tumor angiogenesis, invasion and metastasis, including hepatocellular carcinoma (HCC). Nogo-B is expressed in most tissues and participates in macrophage polarization. However, whether Nogo-B is involved in the polarization and the effects of TAMs has been unclear. The expression of Nogo-B in TAMs of HCC patients is significantly

The lack of available, well characterized, established, domestic porcine cell lines hinders the advancement of porcine cellular immunology. A case of multicentric lymphoma was diagnosed in a market weight pig at the time of slaughter. Affected lymph nodes and spleen were collected and used for single cell isolation and analysis. Cell lines were established by 3 rounds of limiting dilution from splenic

Docetaxel-based chemotherapy is recommended for metastatic castration-resistant prostate cancer (mCRPC). However, chemoresistance is inevitable and eventually progresses after several rounds of chemotherapy. Therefore, exploration of new therapeutic targets and molecular mechanisms that contribute to chemoresistance remains necessary. Our previous study accidentally demonstrated that expression of

PAH is a progressive disease characterized by uncontrolled proliferation of PASMCs. Zinc finger protein A20 is a negative feedback regulatory protein of NF-κB activity. The aim of this study was to evaluate zinc finger protein A20 can alleviate PAH in hypoxia exposed mice. C57BL/6 mice received a tail vein injection of adenovirus-mediated ad-A20 and ad-A20 shRNA were exposed to hypoxia. PASMCs isolated

The formation of de novo centromeres on artificial chromosomes in humans (HACs) and fission yeast (SpYACs) has provided much insights to the epigenetic and genetic control on regional centromere establishment and maintenance. Similarly, the use of artificial chromosomes in point centromeric budding yeast Saccharomyces cerevisiae (ScYACs) and holocentric Caenorhabditis elegans (WACs) has revealed epigenetic

N-alpha-acetyltransferase 80 (NAA80) was recently demonstrated to acetylate the N-terminus of actin, with NAA80 knockout cells showing actin cytoskeleton-related phenotypes, such as increased formation of membrane protrusions and accelerated migration. Here we report that NAA80 knockout cells additionally display fragmentation of the Golgi apparatus. We further employed rescue assays to demonstrate

Recent ribosome profiling and proteomic studies have revealed the presence of thousands of novel coding sequences, referred to as small open reading frames (sORFs), in prokaryotic and eukaryotic genomes. These genes have defied discovery via traditional genomic tools not only because they tend to be shorter than standard gene annotation length cutoffs, but also because they are, as a class, enriched

The degree of polymorphism, i.e., DNA sequence divergence, of short AT-rich tandemly arranged simple sequence repeats at or near promoters and 5′- untranslated regions of mRNA may quantitatively regulate transcription of tissue-specific genes. Less polymorphic repeats allow greater gene expression. Preferential binding of hypophosphorylated H1 histone to these repeats may diminish binding of transcription

EBV-associated gastric carcinoma (EBVaGC) is accompanied by massive lymphocyte infiltration, but therapy resistance and tumor progression still occur in patients with EBVaGC. Cancer stem cells (CSCs) are reported to possess immunomodulatory ability that allows them to resist immune-mediated rejection for many tumor types. However, whether and how CSCs in EBVaGC exhibit immunosuppression has not yet

Human leukocyte antigen (HLA) class I molecules present antigenic peptides to cytotoxic T cells, causing lysis of malignant cells. Transplantation biology studies have implicated HLA class I molecules in cell migration, but there has been little evidence presented that they influence cancer cell migration, a contributing factor in metastasis. In this study, we examined the effect of HLA-B on pancreatic

The endothelial-mesenchymal transition (EndMT) plays a key role in the development of cardiac fibrosis (CF) after acute myocardial infarction (AMI). The results of our previous study showed that amphiregulin (AR) expression was enhanced after MI. However, the role of AR on EndMT post MI remains unknown. This study aimed to elucidate the impact of AR on EndMT post MI and the associated molecular mechanisms

The centromere is the nucleoproteic chromosomal structure necessary for accurate chromosome segregation during cell division. One of the earliest centromeric proteins to be discovered was CENP-B, the only one capable to recognize a specific centromeric DNA binding motif. The phylogenetic history of this protein and of its DNA binding site shows independent events of function acquisition across different

Overexpression of the c-Myc oncogene has been implicated in cancer stem cell - like (CSC) phenotypes and epithelial-to-mesenchymal transition (EMT) in cancer. However, the underlying molecular mechanism by which c-Myc regulates EMT and CSC potential in remains unclear. In the present study, we showed that the expression of c-Myc protein is inversely correlated with microRNA (miR)-200c expression in

BRAF mutations occur in approximately 50% of melanoma patients. The mutated BRAF kinase continuously activates the mitogen-activated protein kinase (MAPK) pathway to promote cell growth and proliferation. Vemurafenib as a specific BRAF inhibitor can significantly prolong progression-free survival in melanoma patients. However, most patients developed resistance to Vemurafenib after 6 months. The mechanism

UAP56 is an essential factor in eukaryotic pre-mRNA splicing and mRNA export. Many viruses require cellular RNA export factors to efficiently export viral RNA. However, the mechanisms behind hepatitis B virus (HBV) RNA splicing and nuclear export remain poorly understood. Here, our data show that UAP56 interacts with the HBx protein. Moreover, we demonstrate that the Q-motif of UAP56, which regulates

Radioresistance observed in patients with colorectal cancer (CRC) may be related to the presence of cancer stem cells (CSCs), but the underlying mechanism(s) remain unclear. Cancer-associated fibroblasts (CAFs) can regulate the stemness of cancer cells and tumor radiosensitivity. In addition, exosomes have been reported to modify treatment response by mediating cell–cell communication. In this study

Tumor-initiating cells (T-ICs) are involved in the tumorigenesis, progression, drug resistance and recurrence of hepatocellular carcinoma (HCC). However, the underlying mechanism for the propagation of liver T-ICs remains unclear. Herein, we find that miR-454 is upregulated in liver T-ICs and has an important function in liver T-ICs. Functional studies have revealed that knockdown of miR-454 inhibits

The ability to redesign and reconstruct a cell at whole-genome level provides new platforms for biological study. The international synthetic yeast genome project-Sc2.0, designed by interrogating knowledge amassed by the yeast community to date, exemplifies how a classical synthetic biology “design-build-test-learn” engineering cycle can effectively test hypotheses about various genome fundamentals

Bone marrow failure is the primary cause of death after nuclear accidents or intentional exposure to high or low doses of ionizing radiation. Hematopoietic stem cell transplantation is the most potent treatment procedure for patients suffering from several hematopoietic malignancies arising after radiation injuries. Successful hematopoietic recovery after transplantation depends on efficient homing

Podocyte injury leads to impaired filtration barrier function of the kidney that underlies the pathophysiology of idiopathic nephrotic syndrome (INS), the most common NS occurring in children. The heat shock protein 90 (Hsp90) is involved in the regulation of apoptosis in a variety of cell types, however, little is known about its role in podocytes and whether it associated with NS. Here, we show that

Tankyrase 1 (TNKS1; PARP-5a) and Tankyrase 2 (TNKS2; PARP-5b) are poly-ADP-ribosyl-polymerase (PARP)-domain-containing proteins that regulate the activities of a wide repertoire of target proteins via post-translational addition of poly-ADP-ribose polymers (PARylation). Although tankyrases were first identified as regulators of human telomere elongation, important and expansive roles of tankyrase activity

Although primary cilia abnormalities have been frequently observed in multiple cancers, including prostate cancer (PCa), the molecular mechanisms underlying primary ciliogenesis repression in PCa cells remain unclear. Transforming acidic coiled-coil protein-3 (TACC3), whose deregulation has been implicated in the pathogenesis of several types of cancer, is a key centrosomal protein that plays a crucial

High throughput RNA sequencing techniques have revealed that a large fraction of the genome is transcribed into long non-coding RNAs (lncRNAs). Unlike canonical protein-coding genes, lncRNAs do not contain long open reading frames (ORFs) and tend to be poorly conserved across species. However, many of them contain small ORFs (sORFs) that exhibit translation signatures according to ribosome profiling

MUC1 is a tumor-associated antigen (TAA) overexpressed in many tumor types, which makes it an attractive target for cancer immunotherapy. However, this marker is a non-mutated antigen without high immunogenicity. In this study, we designed several new altered peptides by replacing amino acids in their sequences, which were derived from a low-affinity MUC1 peptide, thus bypassing immune tolerance. Compared

Pulmonary arterial hypertension (PAH) is closely associated with profound vascular remodeling, especially pulmonary arterial medial hypertrophy and muscularization, due to aberrant proliferation of pulmonary artery smooth muscle cells (PASMCs). Berberine, a drug commonly used to treat inflammation, may be a novel therapeutic option for PAH by improving pulmonary artery remodeling. The present study

The concepts of synthetic biology have the potential to transform plant genetics, both in how we analyze genetic pathways and how we transfer that knowledge into useful applications. While synthetic biology can be applied at the level of the single gene or small groups of genes, this commentary focuses on the ultimate challenge of designing fully synthetic plant chromosomes. Engineering at this scale

Farnesoid X receptor (FXR) is a metabolic nuclear receptor, which protects liver from many endogenous and exogenous injuries. Metallothioneins (MTs) belong to a low-molecular-weight protein family involved in metal homeostasis and the regulation of hepatic oxidative stress. In the present study, we aimed to investigate the effect of FXR on hepatic MT1 expression and the underlying mechanism. C57BL/6

Background Endothelial-to-mesenchymal transition (EndMT) has been implicated in initiation and progression of pulmonary arterial hypertension (PAH). Gremlin-1 promotes vascular remodeling of PAH and mediates epithelial-mesenchymal transition, which is similar to EndMT. In the present study we investigated the potential role of gremlin-1plays in EndMT of pulmonary artery endothelial cells (PAECs). Methods

Patients with estrogen receptor α positive (ERα+) breast cancer can respond to endocrine therapy, but treatment resistance is common and associated with downregulation of ERα expression in the dormant residual cells. Here we show, using long-term NSG xenograft models of human breast cancer and primary human monocytes, in vitro primary cell cultures and tumors from breast cancer patients, that macrophage

MiR-328–3p has been reported to be downregulated and serve as a tumor suppressor in several cancers. Previous studies only have reported the downregulation of miR-328–3p in CRC. However, the roles of miR-328–3p in CRC growth and metastasis were unknown. In this study, we demonstrated that miR-328–3p overexpression inhibited cell proliferation, migration, invasion, and epithelial-mesenchymal transition

“Genomically” humanized animals are invaluable tools for generating human disease models and for biomedical research. Humanized animal models have generally been developed via conventional transgenic technologies; however, conventional gene delivery vectors such as viruses, plasmids, bacterial artificial chromosomes, P1 phase-derived artificial chromosomes, and yeast artificial chromosomes have limitations

Current studies have shown that POTE ankyrin domain family members have high expressions as tumor antigens in malignant tumors, such as prostate cancer, ovarian cancer, breast cancer and the like. POTEE is a member of the POTE anchor protein family E. However, its role in colorectal carcinoma (CRC) has not been studied. In this study, the function of POTEE in CRC was examined for the first time and

The proliferation and migration of Schwann cells contribute to nerve regeneration after peripheral nerve injury (PNI). In recent years, roles of long non-coding RNAs (lncRNAs) in PNI have been gradually uncovered. However, a highly conserved nuclear lncRNA Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in peripheral nerve regeneration remains enigmatic. MALAT1 expression in injured

Growing evidence illustrates the shortcomings on the current understanding of the full complexity of the proteome. Previously overlooked small open reading frames (sORFs) and their encoded microproteins have filled important gaps, exerting their function as biologically relevant regulators. The characterization of the full small proteome has potential applications in many fields. Continuous development

Cellular senescence is a phenomenon of irreversible growth arrest of mammalian somatic cells. Senescent cells increase the production of secretory proteins such as inflammatory cytokines, a phenomenon termed senescence-associated secretory phenotype (SASP). SASP is known to have profound effects on organismal health and aging; however, the molecular mechanisms of SASP are not precisely understood.

After the construction of genomic libraries with yeast artificial chromosomes in the late 1980's for gene isolation and expression studies in cells, human artificial chromosomes were then a natural development in the 1990's, based on the same principles of formation requiring centromeric sequences for generating functional artificial chromosomes. Over the past twenty years, they became a useful research

Tissue inhibitor of metalloproteinase 1 (TIMP1) has various biological activities including the regulation of cell growth and differentiation. However, its role in bone homeostasis and remodeling remains poorly understood. In this study, we investigated the effects of TIMP1 on osteoblast and osteoclast activity at both cellular and molecular level using siRNA-mediated knockdown techniques. Our results

Autophagy is an intracellular degradation pathway that is highly conserved during the evolution of eukaryotes and is based on lysosome. Under nutritional deficiencies or stress, cells can clear damaged and necrotic organelles and proteins through autophagy to maintain the homeostasis of cells and organisms. Studies have found that abnormal autophagy is closely related to the occurrence and development

Concomitant treatment with deferoxamine (DFO) protects neural cells from iron and heme-mediated oxidative injury, but also disrupts cell responses to iron loading that may be protective. We hypothesized that DFO treatment and withdrawal would subsequently increase neuronal vulnerability to hemoglobin. Pretreatment with DFO followed by its washout increased neuronal loss after subsequent hemoglobin

Pluripotent cells transiently develop during peri-implantation embryogenesis and have the capacity to convert into three embryonic lineages. Two typical states of pluripotency, naïve and primed, can be experimentally induced in vitro. The in vitro naïve state can be stabilized in response to environmental inductive cues via a unique transcriptional regulatory program. However, interference with various

Chromosomes and chromosomal gene delivery vectors, human/mouse artificial chromosomes (HACs/MACs), can introduce megabase-order DNA sequences into target cells and are used for applications including gene mapping, gene expression control, gene/cell therapy, and the development of humanized animals and animal models of human disease. Microcell-mediated chromosome transfer (MMCT), which enables chromosome

Since epigenetic modifications are a key driver for cellular differentiation, the regulation of these modifications is tightly controlled. Interestingly, recent studies have revealed metabolic regulation for epigenetic modifications in pluripotent cells. As metabolic differences are prominent between naive (pre-implantation) and primed (post-implantation) pluripotent cells, the epigenetic changes regulated

Phospholipid Phosphatase-Related Protein Type 1 (PLPPR1) is a six-transmembrane protein that belongs to the family of plasticity-related gene proteins, which is a novel brain-specific subclass of the lipid phosphate phosphatase superfamily. PLPPR1-5 have prominent roles in synapse formation and axonal pathfinding. We found that PLPPR1 overexpression in the mouse neuroblastoma cell line (Neuro2a) results

The duplication and segregation of the genome during cell division is crucial to maintain cell identity, development of organisms and tissue maintenance. Centromeres are at the basis of accurate chromosome segregation as they define the site of assembly of the kinetochore, a large complex of proteins that attaches to spindle microtubules driving chromosome movement during cell division. Here we summarize

Both embryo-derived (ESC) and induced pluripotent stem cell (iPSC) lines have been established in rabbit. They exhibit the essential characteristics of primed pluripotency. In this review, we described their characteristic features at both molecular and functional levels. We also described the attempts to reprogram rabbit pluripotent stem cells (rbPSCs) toward the naive state of pluripotency using

Centromeres are highly specialized genomic loci that function during mitosis to maintain genome stability. Formed primarily on repetitive α-satellite DNA sequence characterisation of native centromeric chromatin structure has remained challenging. Fortuitously, neocentromeres are formed on a unique DNA sequence and represent an excellent model to interrogate centromeric chromatin structure. This review

The a3 isoform of vacuolar-type proton-pumping ATPase (V-ATPase) is essential for bone resorption by osteoclasts. Although more than 90 mutations of the human a3 gene have been identified in patients with infantile malignant osteopetrosis, it is unclear whether they lead to osteoclast dysfunction. We have established an in vitro assay to induce osteoclasts from spleen macrophages derived from a3-knockout

The centromere is a specialized chromosomal locus required for accurate chromosome segregation. Heterochromatin also assembles around centromere chromatin and forms a base that supports sister chromatid cohesion until anaphase begins. Both centromere chromatin and heterochromatin assemble on a centromeric DNA sequence, a highly repetitive sequence called alphoid DNA (α-satellite DNA) in humans. Alphoid

Centromeres are central to chromosome segregation and genome stability, and thus their molecular foundations are important for understanding their function and the ways in which they go awry. Human centromeres typically form at large megabase-sized arrays of alpha satellite DNA for which there is little genomic understanding due to its repetitive nature. Consequently, it has been difficult to achieve

Centromeres are the eukaryotic chromosomal sites at which the kinetochore forms and attaches to spindle microtubules to orchestrate chromosomal segregation in mitosis and meiosis. Although centromeres are essential for cell division, their sequences are not conserved and evolve rapidly. Centromeres vary dramatically in size and organization. Here we categorize their diversity and explore the evolutionary