A5103120728- Cellular transport and secretion
- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- MicroRNA in disease regulation
- RNA Research and Splicing
- Cancer Cells and Metastasis
- Genetics, Aging, and Longevity in Model Organisms
- Circular RNAs in diseases
- Cancer, Hypoxia, and Metabolism
- Endoplasmic Reticulum Stress and Disease
- Ubiquitin and proteasome pathways
- Graphene and Nanomaterials Applications
- Nanoparticles: synthesis and applications
- Phagocytosis and Immune Regulation
- Microbial metabolism and enzyme function
- Cancer Research and Treatments
- Microtubule and mitosis dynamics
- Mechanisms of cancer metastasis
- Wnt/β-catenin signaling in development and cancer
- Microplastics and Plastic Pollution
- Circadian rhythm and melatonin
- S100 Proteins and Annexins
- Anesthesia and Neurotoxicity Research
- Epigenetics and DNA Methylation
- Porphyrin Metabolism and Disorders
The University of Texas MD Anderson Cancer Center
2016-2024
Jiangnan University
2023-2024
Tulane University
2024
Thoracic Surgery Foundation
2016-2018
Chinese Academy of Medical Sciences & Peking Union Medical College
2012-2017
The University of Texas Health Science Center at Houston
2014
Tsinghua University
2012
Gliomas are the most common and deadly type of primary brain tumor. In this study, we showed that cAMP response element-binding protein (CREB), a proto-oncogenic transcription factor is overexpressed in gliomas, can promote gliomagenesis by modulating expression oncogenic microRNA-23a (mir-23a). First, found CREB highly expressed glioma tissues cell lines. also essential for growth survival vitro critical vivo. Second, microRNA microarray, ChIP-chip, ChIP-quantitative PCR, luciferase...
Epithelial tumor cells that have undergone epithelial-to-mesenchymal transition (EMT) are typically prone to metastasis and drug resistance contribute a poor clinical outcome. The transcription factor ZEB1 is known driver of EMT, mediators represent potential therapeutic targets for suppression. Here, we shown phosphatidylinositol 3-kinase-targeted (PI3K-targeted) therapy suppresses in mouse model Kras/Tp53-mutant lung adenocarcinoma develops metastatic disease due high expression ZEB1. In...
Tumor cells gain metastatic capacity through a Golgi phosphoprotein 3–dependent (GOLPH3-dependent) membrane dispersal process that drives the budding and transport of secretory vesicles. Whether underlies pro-metastatic vesicular trafficking is associated with epithelial-to-mesenchymal transition (EMT) remains unclear. Here, we have shown that, rather than causing dispersal, EMT led to formation compact organelles improved ribbon linking cisternal stacking. Ectopic expression EMT-activating...
Three miR-34 family members (miR-34a, miR-34b, and miR-34c) are clustered on two different chromosomal loci, Mir34a Mir34b/c. These miRNAs have identical seed sequences, which predicted to target the same set of genes. However, miR-34a miR-34c sets negatively correlated genes in lung adenocarcinoma data from The Cancer Genome Atlas. Therefore, we hypothesized that individual members, tumor suppressive miRNAs, would varying effects tumorigenesis. To show this, overexpressed each cluster...
Migration-proliferation dichotomy is a common mechanism in gliomagenesis; however, an understanding of the exact molecular this "go or grow" phenomenon remains largely incomplete. In present study, we first found that microRNA-9 (miR-9) highly expressed glioma cells. MiR-9 inhibited proliferation and promoted migration cells by directly targeting cyclic AMP response element-binding protein (CREB) neurofibromin 1 (NF1), respectively. Our data also suggested migration-inhibitory role for CREB...
Although the roles of circadian Clock genes and microRNAs in tumorigenesis have been profoundly studied, mechanisms cross‐talk between them regulation gliomagenesis are poorly understood. Here we show that expression level CLOCK is significantly increased high‐grade human glioma tissues glioblastoma cell lines. In contrast miR‐124 attenuated similar samples. Further studies a direct target miR‐124, either restoration or silencing can reduce activation NF‐κB. conclusion, suggest as suppressor...
Epithelial tumor cells undergo epithelial-to-mesenchymal transition (EMT) to gain metastatic activity. Competing endogenous RNAs (ceRNAs) have binding sites for a common set of microRNAs (miRs) and regulate each other's expression by sponging miRs. Here, we address whether ceRNAs govern metastasis driven the EMT-activating transcription factor ZEB1. High miR-181b levels were correlated with an improved prognosis in human lung adenocarcinomas, cell lines derived from murine adenocarcinoma...
This study identifies a molecular basis for malignant secretion and provides rationale to test PI4KIIIβ antagonists as an intervention.
Lysyl hydroxylase 2 (LH2) is highly expressed in multiple tumor types and accelerates disease progression by hydroxylating lysine residues on fibrillar collagen telopeptides to generate stable cross links stroma. Here, we show that a galactosylhydroxylysyl glucosyltransferase (GGT) domain LH2-modified type-VI (Col6) promote lung adenocarcinoma (LUAD) growth metastasis. In tumors generated LUAD cells lacking LH2 GGT activity, stroma was less stiff, of were reduced. Mass spectrometric analysis...
Abstract Background microRNAs (miRNAs) are shown to be involved in the regulation of circadian clock. However, it remains largely unknown whether miRNAs can regulate core clock genes ( Clock and Bmal1 ). Results In this study, we found that mir-142-3p directly targeted 3’UTR human BMAL1 mouse . The over-expression (in 293ET NIH3T3 cells) knockdown U87MG reduced up-regulated Bmal1/BMAL1 mRNA protein levels, respectively. Moreover, expression level oscillated serum-shocked cells results ChIP...
Abstract Collagen lysyl hydroxylases (LH1-3) are Fe 2+ - and 2-oxoglutarate (2-OG)-dependent oxygenases that maintain extracellular matrix homeostasis. High LH2 levels cause stable collagen cross-link accumulations promote fibrosis cancer progression. However, developing LH antagonists will require structural insights. Here, we report a 2 Å crystal structure X-ray scattering on dimer assemblies for the domain of L230 in Acanthamoeba polyphaga mimivirus . Loop residues double-stranded β-helix...
// Xihua Lin 1 , Bin Yang Wei Liu Xiaochao Tan 3 Fan Wu Peishan Hu Tao Jiang 2 Zhaoshi Bao Jiangang Yuan Boqin Qiang Xiaozhong Peng and Han Institute of Basic Medical Sciences Chinese Academy Sciences, School Medicine Peking Union College, Beijing, China Department Neurosurgery, Beijing Tiantan Hospital, Capital University, Thoracic/Head Neck Oncology, University Texas MD Anderson Cancer Center, Houston, Texas, USA Correspondence to: Han, email: Peng, Keywords : PCBP2, ARHGDIA, miRNA,...
Therapeutic strategies designed to target TP53-deficient cancer cells remain elusive. Here, we showed that TP53 loss initiated a pharmacologically actionable secretory process drove lung adenocarcinoma (LUAD) progression. Molecular, biochemical, and cell biological studies increased the expression of Golgi reassembly stacking protein 55 kDa (G55), maintains organelle integrity is part GOLGIN45 (G45)-myosin IIA-containing complex activates vesicle biogenesis in Golgi. activated G55-dependent...
Abstract Epithelial-to-mesenchymal transition (EMT) is a transcriptionally governed process by which cancer cells establish front-rear polarity axis that facilitates motility and invasion. Dynamic assembly of focal adhesions other actin-based cytoskeletal structures on the leading edge motile requires precise spatial temporal control protein trafficking. Yet, way in EMT-activating transcriptional programs interface with vesicular trafficking networks effect cell change remains unclear. Here,...
Epithelial-to-mesenchymal transition (EMT) underlies immunosuppression, drug resistance, and metastasis in epithelial malignancies. However, the way which EMT orchestrates disparate biological processes remains unclear. Here, we identify an EMT-activated vesicular trafficking network that coordinates promigratory focal adhesion dynamics with immunosuppressive secretory program lung adenocarcinoma (LUAD). The EMT-activating transcription factor ZEB1 drives exocytotic by relieving Rab6A,...
It has been reported that ubiquitin-conjugating enzyme 9 (Ubc9), the unique enzyme2 in sumoylation pathway, is up-regulated many cancers. However, expression and regulation of UBC9 glioma remains unknown. In this study, we found Ubc9 was tissues cell lines compared to a normal control. knockdown by small interfering RNA (siRNA) affected proliferation apoptosis T98G cells. Further experiments revealed microRNA (miR)-214 directly targeted 3' untranslated region (UTR) there an inverse...
Hypersecretory malignant cells underlie therapeutic resistance, metastasis, and poor clinical outcomes. However, the molecular basis for hypersecretion remains obscure. Here, we showed that epithelial-mesenchymal transition (EMT) initiates exocytic endocytic vesicular trafficking programs in lung cancer. The EMT-activating transcription factor zinc finger E-box-binding homeobox 1 (ZEB1) executed a PI4KIIIβ-to-PI4KIIα (PI4K2A) dependency switch drove PI4P synthesis Golgi endosomes. EMT...
Cancer cells exhibit heightened secretory states that drive tumor progression. Here, we identify a chromosome 3q amplicon serves as platform for regulation in cancer. The encodes multiple Golgi-resident proteins, including the scaffold Golgi integral membrane protein 4 (GOLIM4) and ion channel ATPase Secretory Pathway Ca2+ Transporting 1 (ATP2C1). We show GOLIM4 recruits ATP2C1 phosphoprotein 3 (GOLPH3) to coordinate calcium-dependent cargo loading bending vesicle scission. depletion...
Cancer cells are a major source of enzymes that modify collagen to create stiff, fibrotic tumor stroma. High lysyl hydroxylase 2 (LH2) expression promotes metastasis and is correlated with shorter survival in lung adenocarcinoma (LUAD) other types. LH2 hydroxylates lysine (Lys) residues on fibrillar collagen's amino- carboxy-terminal telopeptides stable cross-links. Here, we show electrostatic interactions between the LH domain active site determine unique telopeptidyl (tLH) activity LH2....
Cancer cells exhibit hyperactive secretory states that maintain cancer cell viability and remodel the tumor microenvironment. However, oncogenic signals heighten secretion remain unclear. Here, we show p53 loss activates prometastatic vesicle biogenesis in Golgi. up-regulates expression of a Golgi scaffolding protein, progestin adipoQ receptor 11 (PAQR11), which recruits an adenosine diphosphate ribosylation factor 1-containing protein complex loads cargos into vesicles. PAQR11-dependent...
The possible toxicity caused by nanoplastics or microplastics on organisms has been extensively studied. However, the unavoidably combined effects of and organisms, particularly intestinal toxicity, are rarely clear. Here, we employed
In the real environment, some chemical functional groups are unavoidably combined on nanoplastic surface. Reportedly, amino-modified polystyrene nanoparticles (PS-A NPs) exposure in parents can induce severe transgenerational toxicity, but underlying molecular mechanisms remain largely unclear. Using Caenorhabditis elegans as animal model, this study was performed to investigate role of germline epidermal growth factor (EGF) signal modulating PS-A NPs' toxicity. As a result, 1–10 μg/L NPs...