Biology subjects

Liu, y.

Publications and source records attributed to Liu, y..

5 recordsLinked to original sources

bioRxiv2024

Haplotype-resolved assemblies provide insights into genomic makeup of the oldest grapevine cultivar (Munage) in Xingjiang

AbstractsMunage, an ancient grape variety that has been cultivated for thousands of years in Xinjiang, China, is recognized for its exceptional fruit traits. There are two main types of Munage: white fruit (WM) and red fruit (RM). However, the lack of a high-quality genomic resources has impeded effective breeding and restricted the potential for expanding these varieties to other growing regions. In this study, we assembled haplotype-resolved genome assemblies for WM and RM, alongside integrated whole genome resequencing (WGS) data and transcriptome data to illuminate specific mutations and associated genes in Munake and the genes associated with fruit color traits. Selective analysis between Munage clones and Eurasian grapes suggested that adaptive selection exists in Munage grapes, with genes enriched in processes including cell maturation, plant epidermal cell differentiation, and root epidermal cell differentiation. The study examined the mutations within Munage grapes and found that the genes PMAT2 on chromosome 12 and MYB123 on chromosome 13 are likely responsible for color variation in RM. These findings provide crucial genetic resources for investigating the genetics of the ancient Chinese grape variety, Munage, and will facilitate the genetic improvement in grapevine.

genomics↗

bioRxiv2024

Glioma-associated fibroblasts promote glioblastoma resistance to temozolomide through CCL2-CCR2 paracrine signaling

Complicated tumor microenvironment contributes mostly to chemoresistance in glioblastoma. Glioma-associated fibroblasts (GAFs) were recently identified as non-tumor stromal cells in the glioblastoma microenvironment, whereas their function in glioblastoma chemoresistance is unclear. Herein, we interrogated the correlation between GAFs and chemoresistance of glioblastoma by examining a series of patient-derived GAFs and glioblastoma organoids (GBOs), revealing that GAFs could promote temozolomide resistance in glioblastoma. Mechanistically, C-C motif chemokine ligand 2 (CCL2) secreted by GAFs selectively activated the ERK1/2 signaling in glioblastoma cells to potentiate temozolomide resistance. Pharmacologically disrupting the CCL2-CCR2 axis or MEK1/2-ERK1/2 pathway effectively improved the therapeutic efficacy of temozolomide in GBM cells and patient-derived GBOs, and both decreased phospho-ERK1/2 expression. Collectively, our results identified that targeting the GAF-dominated CCL2-ERK1/2 pathway may be an alternative strategy to alleviate the GAF-mediated chemoresistance of glioblastoma. SignificanceComprehensive interpretation of the mutual support between tumor microenvironment and cancer cells is demanded for glioma with poor response rates to chemotherapy. This study demonstrates that GAFs promote the temozolomide resistance of glioblastoma by secreting cytokine CCL2 to activate ERK1/2 pathway, which may serve as a potential druggable candidate. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=140 SRC="FIGDIR/small/581575v1_ufig1.gif" ALT="Figure 1"> View larger version (50K): org.highwire.dtl.DTLVardef@167b955org.highwire.dtl.DTLVardef@b892bcorg.highwire.dtl.DTLVardef@1a9b082org.highwire.dtl.DTLVardef@18327a8_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphic abstract.C_FLOATNO Schematic illustration for GAFs mediated chemoresistance of GBMs and underlying mechanisms. We demonstrate that Glioma-associated Fibroblasts (GAFs) grow in gliomas by isolating and identifying a panel of patient-derived GAFs. CCL2 secreted by GAFs stimulates CCR2 in GBM cells, which promotes activation of the ERK1/2 expression to potentiate GBM chemoresistance. C_FIG

cancer biology↗

bioRxiv2022

SP1 affects the migration and invasion of laryngeal cancer cells by regulating methylation of claudin 4 promoter region through the p-JNK pathway

Claudin 4 (CLDN4) is abnormally expressed in various tumors, but the mechanisms controlling CLDN4 expression in laryngeal cancer are poorly understood. Here, we describe hypermethylation of the promoter region of the CLDN4 gene and a positive correlation between the expression of CLDN4 and transcription factor Sp1 in laryngeal carcinoma. Specifically, CLDN4 expression was downregulated when laryngeal cancer cells were treated with Sp1 transcription factor inhibitor MTM. Immunohistochemical staining showed that while the expression of CLDN4 and p-JNK was negatively correlated, p-JNK positively correlated with MMP-2 and MMP-9 expression. The expressions of p-JNK, MMP-2, and MMP-9 were significantly downregulated in HEp-2 cells transfected with CLDN4, decreasing migration and invasiveness of HEp-2 cells. Thus, we show that SP1-mediated hypermethylation of the CLDN4 promoter region may activate the JNK signaling pathway and increase MMP-2/MMP-9 expression, which can then affect the migration and invasiveness of laryngeal cancer cells. These results contribute to our understanding of the regulatory mechanisms of CLDN4 in laryngeal cancer and identify the Sp1-CLDN4-jnk signaling pathway-MMP-2/MMP-9 axis as a potential target for the treatment of laryngeal cancer.

cancer biology↗

bioRxiv2020

Mining the potential of VRS1-5 gene to raise barley grain yield

VRS1-5 genes determine spike row types during the early stages of spike development in barley (Hordeum vulgare), yet their functions for the determination of grain yield during the late stages of spike development are largely unknown. To assess the role of VRS1-5 genes in determining grain yield components, we sequenced VRS1-5 genes from 894 worldwide barley accessions and measured 19 spike morphology traits in four environments. Single nucleotide polymorphism SNP markers and gene marker-based haplotypes for VRS1-5 displayed close associations with spike morphology traits. We further developed a spatiote-temporal transcriptome atlas (255 samples) at 17 stages and five positions along the spike, that linked spike morphology to spikelet development and expression patterns of VRS1-5 genes. Phenotypic measurements demonstrated that mutations in VRS1-5 suppress the initiation of spikelet primordia and, trigger spikelet abortion by increasing cytokinin content and improving sensitivity of spikelet primordia to cytokinin. Our integrated results illustrate how breeding can globally alter spike morphology through diversity at the VRS1-5 genes, which show great potential in increasing barley grain yield.

developmental biology↗

bioRxiv2019

The characterization of a humanized rabbit anti-TNF α monoclonal antibody?A nationwide RA treatment drug study

Tumor necrosis factor alpha (TNF) is now regarding as a key role in the pathogenesis of immune-mediated disease such as Rheumatoid arthritis (RA), Crohn's Disease, Psoriatic arthritis and Plaque Psoriasis. HERE we have successfully developed an anti-hTNF monoclonal rabbit antibody(HZ3M) with high binding and neutralizing activity based on RabMAbs platform. Rabbit hybridomas, immunized subcutanrously with 0.4 mg human TNF, were generated from the rabbit splenocytes and a total of 142 hybridoma clones with specific binding to human TNFa were obtained. The anti-TNFa RabMAbs showed better neutralizing activity and higher antigen binding affinity compared to Humira and Remicade, the elimination phase half-life 58.2h respectively. In vivo efficay studies, normal mice or human TNF-alpha transgenic mice were injected with 1.0 mg/kg Humira (positive control), HZ3M at 0.33?1.0 or 3.0 mg/kg, or solvent (negative control), showed that HZ3M is able to bind and neutralize hTNF in transgenic and normal mice as well as normal rabbits.Clearly dose-dependent response can be determined. Compared to marketed anti-TNFa drug Humira, the efficacy of HZ3M is seems to show significant longer holding time.Our observations indicate that the HZ3M derived from RabMAb preclinical safety study, and might have a therapeutic role in RA treatment.

cell biology↗