Biology subjects

Zhong, C.

Publications and source records attributed to Zhong, C..

At least 55 records · Page 3Linked to original sources

bioRxiv2021

The supramolecular organization of SARS-CoV and SARS-CoV-2 virions revealed by coarse-grained models of intact virus envelopes

The coronavirus disease 19 (COVID-19) pandemic is causing a global health crisis and has already caused a devastating societal and economic burden. The pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has a high sequence and architecture identity with SARS-CoV, but far more people have been infected by SARS-CoV-2. Here, combining structural data from cryo-EM and structure prediction, we constructed bottom-up Martini coarse-grained models of intact SARS-CoV and SARS-CoV-2 envelopes. Microsecond molecular dynamics simulations were performed, allowing us to explore their dynamics and supramolecular organization. Both SARS-CoV and SARS-CoV-2 envelopes present a spherical morphology with structural proteins forming multiple string-like islands in the membrane and clusters between heads of spike proteins. Critical differences between the SARS-CoV and SARS-CoV-2 envelopes are the interaction pattern between spike proteins and the flexibility of spike proteins. Our models provide structural and dynamic insights in the SARS virus envelopes, and could be used for further investigation, such as drug design, and fusion and fission processes.

biophysics↗

bioRxiv2021

A histidine cluster determines YY1-compartmentalized coactivators and chromatin elements in phase-separated super-enhancers

As an oncogenic transcription factor, Yin Yang 1 (YY1) regulates enhancer and promoter connection. However, gaps still exist in understanding how YY1 coordinates coactivators and chromatin elements to assemble super-enhancers. Here, we demonstrate that YY1 activates FOXM1 gene expression through forming liquid-liquid phase separation to compartmentalize both coactivators and enhancer elements. In the transactivation domain of YY1, a histidine cluster is essential for its activities of forming phase separation, which can be extended to additional proteins. Coactivators EP300, BRD4, MED1 and active RNA polymerase II are components of YY1-rich nuclear puncta. Consistently, histone markers for gene activation, but not repression, colocalize with YY1. Importantly, multiple enhancer elements and the FOXM1 promoter are bridged by YY1 to form super-enhancers. These studies propose that YY1 is a general transcriptional activator, and promotes phase separation with incorporation of major coactivators and stabilization by distal enhancers to activate target gene expression.

cell biology↗

bioRxiv2021

Engineered Bacteriophage T4 Nanoparticle as a Potential Targeted Activator of HIV-1 Latency in CD4+ Human T cells

A major barrier for HIV-1 eradication is the latent virus reservoir containing stably integrated and silent proviruses in CD4+ T-cells. Targeted reactivation and removal of this latent reservoir is a potential strategy for HIV-1 cure but remains a major challenge. Here, we investigated whether CD4-targeted bacteriophage T4 capsid nanoparticles that mimic HIV envelope can reactivate HIV-1 latency. The nanoparticles were arrayed with CD4-binding CD4-DARPin, or HIV-1 gp140 envelope trimer. When exposed to J-Lat T-cell model of HIV-1 latency or primary T-lymphocytes from human PBMCs, these nanoparticles activated CD4+ T-cells without causing global T-cell activation, which led to activation of HIV-1 proviral transcription, viral protein production and release. Intriguingly, the observed T-cell activation and HIV-1 latency reversal do not involve the classic PKC or NFAT pathways and did not lead to cytokine storm. These studies indicate that engineered non-infectious bacteriophages can be exploited for HIV-1 cure and targeted T-cell therapies.

immunology↗

bioRxiv2021

Key Promoter Region of Wnt4 response to FSH and Genetic Effect on Several Production Traits of Its Mutations in Chicken

The signaling pathway of the wingless-type mouse mammary tumor virus integration site (Wnt) plays an important role in ovarian and follicular development. Wnt4 was shown in our previous study to be involved in the selection and development of chicken follicles by up-regulating the expression of follicle stimulating hormone receptors (FSHR), stimulating the proliferation of follicular granulosa cells and increasing the secretion of steroidal hormones. To further characterize cis-elements regulating chicken Wnt4 transcription, in this study we determined critical regulatory regions affecting chicken Wnt4 transcription, then identified a single nucleotide polymorphism (SNP) in this region, and finally analyzed the association of the SNP with chicken production traits. The results showed that the 5' regulatory region from -3354 to -2689 of the chicken Wnt4 gene had the strongest activity and greatest response to FSH stimulation, and that one SNP site -3015 (G > C) in this segment was identified as affecting the binding of NFAT5 (nuclear factor of activated T cells 5). When G was replaced by C at this site, it eliminated the binding by NFAT5. Moreover, this locus was significantly associated with the keel length and comb length of hens. Individuals with the genotype CG had longer keels while those with genotype CC had longer combs. Collectively, these data suggested that the SNP-3015 (G > C) is (i) involved in the regulation of Wnt4 gene expression by affecting the binding of NFAT5, (ii) associated with chicken keel length and comb length, and (iii) is a potential DNA marker in the molecular breeding of chickens for egg laying.

genetics↗

bioRxiv2021

Basal forebrain cholinergic neurons are part of the threat memory engram

Although the engagement of cholinergic signaling in threat memory is well established (Knox, 2016a), our finding that specific cholinergic neurons are requisite partners in a threat memory engram is likely to surprise many. Neurons of the basal forebrain nucleus basalis and substantia innominata (NBM/SIp) comprise the major source of cholinergic input to the basolateral amygdala (BLA), whose activation are required for both the acquisition and retrieval of cued threat memory and innate threat response behavior. The retrieval of threat memory by the presentation of the conditioning tone alone elicits acetylcholine (ACh) release in the BLA and the BLA-projecting cholinergic neurons manifest immediate early gene responses and display increased intrinsic excitability for 2-5 hours following the cue-elicited memory response to the conditioned stimulus. Silencing cue-associated engram-enrolled cholinergic neurons prevents the expression of the defensive response and the subset of cholinergic neurons activated by cue is distinct from those engaged by innate threat. Taken together we find that distinct populations of cholinergic neurons are recruited to signal distinct aversive stimuli via the BLA, demonstrating exquisite, functionally refined organization of specific types of memory within the cholinergic basal forebrain.

neuroscience↗

bioRxiv2021

Methylation of KRAS at lysine 182 and 184 by SETD7 promotes KRAS degradation

Oncogenic KRAS mutations are considered to be a key driver for initiation and progression in non-small-cell lung cancer (NSCLC). However, how post-translational modifications (PTMs) of KRAS, especially methylation, modify KRAS activity and downstream signals remain largely unclear. Here, we showed that SET domain containing histone lysine methyltransferase 7 (SETD7) interacts with KRAS and methylates KRAS at lysine 182 and 184. SETD7-mediated methylation of KRAS led to degradation of KRAS and attenuation of the RAS/MEK/ERK signaling cascade, endowing SETD7 with a potent tumor-suppressive role in NSCLC, both in vitro and in vivo. Mechanistically, RABGEF1, a ubiquitin E3 ligase of KRAS, was recruited and promoted KRAS degradation in a K182/K184 methylation-dependent manner. Notably, low SETD7 or RABGEF1 expression was associated with poor prognosis in lung adenocarcinoma patients. Taken together, our results establish a novel connection between lysine methylation and KRAS protein stability, in addition to elucidating a tumor-suppressive function of SETD7 that operates via modulation of oncogenic RAS signaling.

cancer biology↗

bioRxiv2020

A high-quality genome of the mangrove Aegiceras corniculatum aids investigation of molecular adaptation to intertidal environments

Mangroves have colonized extreme intertidal environments characterized by high salinity, hypoxia, and other abiotic stresses. During millions of years of evolution, mangroves have adapted to these habitats, evolving a series of highly specialized traits. Aegiceras corniculatum, a pioneer mangrove species that evolved salt secretion and crypto-vivipary, is an attractive ecological model to investigate molecular mechanisms underlying adaptation to intertidal environments. Here we report a high-quality reference genome of A. corniculatum using the PacBio SMRT sequencing technology, comprising 827 Megabases (Mb) and containing 32,092 protein-coding genes. The longest scaffold and N50 for the assembled genome are 13.76 Mb and 3.87 Mb. Comparative and evolutionary analyses revealed that A. corniculatum experienced a whole-genome duplication (WGD) event around 35 million years ago after the divergence between Aegiceras and Primula. We inferred that maintenance of cellular environmental homeostasis is an important adaptive process in A. corniculatum. The 14-3-3 protein-coding genes were retained after the recent WGD event, decoding a calcium signal to regulate Na+ homeostasis. A. corniculatum has more H+-ATPase coding genes, essential for the maintenance of low Na+ concentration in the cells, than its relatives. Photosynthesis and oxidative-phosphorylation pathways are overrepresented among significantly expanded gene families and might supply the energy needed for salt secretion. Genes involved in natural antioxidant biosynthesis, contributing to scavenging reactive oxygen species against high salinity, have also increased in copy number. We also found that all homologs of DELAY OF GERMINATION1 (DOG1), a pivotal regulator of seed dormancy, lost their heme-binding ability in A. corniculatum. This loss may contribute to crypto-vivipary. Our study provides a valuable resource to investigate molecular adaptation to extreme environments in mangroves.

genomics↗

bioRxiv2020

Metagenomic Noncoding RNA Profiling and Biomarker Discovery

Noncoding RNA plays important regulatory and functional roles in microorganisms, such as gene expression regulation, signaling, protein synthesis, and RNA processing. Given its essential role in microbial physiology, it is natural to question whether we can use noncoding RNAs as biomarkers to distinguish among environments under different biological conditions, such as those between healthy versus disease status. The current metagenomic sequencing technology primarily generates short reads, which contain incomplete structural information that may complicate noncoding RNA homology detection. On the other hand, de novo assembly of the metagenomics sequencing data remains fragmentary and has a risk of missing low-abundant noncoding RNAs. To tackle these challenges, we have developed DRAGoM (Detection of RNA using Assembly Graph from Metagenomics data), a novel noncoding RNA homology search algorithm. DRAGoM operates on a metagenome assembly graph, rather than on unassembled reads or assembled contigs. Our benchmark experiments show DRAGoMs improved performance and robustness over the traditional approaches. We have further demonstrated DRAGoMs real-world applications in disease characterization via analyzing a real case-control gut microbiome dataset for Type-2 diabetes (T2D). DRAGoM revealed potential ncRNA biomarkers that can clearly separate the T2D gut microbiome from those of healthy controls. DRAGoM is freely available from https://github.com/benliu5085/DRAGoM.

bioinformatics↗

bioRxiv2020

Network-based cancer gene relationship prediction method reveals perturbations in the cancer gene network

The perturbations of protein-protein interactions (PPIs) were found to be the main cause of cancer. Previous gene relationship prediction methods which were trained with non-disease gene interaction data were not compatible to map the PPI network in cancer. Therefore, we established a novel cancer specific PPI prediction method dubbed NECARE, which was based on relational graph convolutional network (R-GCN) with knowledge-based features. It achieved the best performance with a Matthews correlation coefficient (MCC) = 0.84{+/-}0.03 and an F1 = 91{+/-}2% comparing with other methods. With NECARE, we mapped the cancer interactome atlas and revealed that the perturbations of PPIs were enriched on 1362 genes, which were named cancer hub genes. Those genes were found to over-represent with mutations occurring at protein-macromolecules binding interfaces. Furthermore, over 42% of cancer treatment-related genes belonged to hub genes, which were significantly related to the prognosis of 32 types of cancers. Finally, by coimmunoprecipitation, we confirmed that the NECARE prediction method was highly reliable with a 90% accuracy. Overall, we provided the novel network-based protein-protein interaction prediction method and mapped the perturbation of cancer interactome. NECARE is available at: https://github.com/JiajunQiu/NECARE.

bioinformatics↗

bioRxiv2020

Thiamine pyrophosphokinase deficiency induces Alzheimer's pathology

BackgroundThiamine diphosphate (TDP) reduction plays an important role in cerebral glucose hypometabolism, the neurodegenerative indicator, in Alzheimers disease (AD). The mechanism underlying TDP reduction remains elusive. Thus, it is critical to define the mechanism and its effect on neurodegeneration, the pathological basis of the disease occurrence and progression. MethodsThe mRNA levels of all known genes associated with thiamine metabolism, including thiamine pyrophosphokinase (TPK), Solute Carrier Family 19 Member 2 (SLC19A2), SLC19A3, and SLC25A19, in brain samples of patients with AD and other neurodegenerative disorders in multiple independent datasets were analyzed. TPK protein levels were further examined in the brain tissues of AD patients and control subjects. A mouse model with conditional knockout (cKO) of TPK gene in the excitatory neurons of adult brain was established. ResultsThe brain TPK mRNA level was markedly lower in AD patients, but not in other neurodegenerative disorders. The brain TPK protein level was also significantly decreased in AD patients. TPK gene knockout in the mice caused cerebral glucose hypometabolism, {beta}-amyloid deposition, Tau hyperphosphorylation, neuroinflammation, and neuronal loss and brain atrophy. Cross-species correlation analysis revealed the similar changes of gene profiling between the cKO mice and AD patients. ConclusionsThe deficiency of brain TPK, a key enzyme for TDP synthesis, is specific to AD. The cKO mice show AD-associated phenotypes and could serve as a new mouse model for AD studies. Our study provides a novel insight into the critical role of TPK in AD pathogenesis and its potential for the disease treatment.

neuroscience↗

bioRxiv2020

The long non-coding RNA lnc-HLX-2-7 is oncogenic in group 3 medulloblastomas

BackgroundMedulloblastoma (MB) is an aggressive brain tumor that predominantly affects children. Recent high-throughput sequencing studies suggest that the non-coding RNA genome, in particular long non-coding RNAs (lncRNAs), contributes to MB sub-grouping. Here we report the identification of a novel lncRNA, lnc-HLX-2-7, as a potential molecular marker and therapeutic target in group 3 MBs. MethodsPublicly available RNA sequencing (RNA-seq) data from 175 MB patients were interrogated to identify lncRNAs that differentiate between MB subgroups. After characterizing a subset of differentially expressed lncRNAs in vitro and in vivo, the group 3-enriched lncRNA lnc-HLX2-7 was deleted by CRISPR/Cas9 in the MB cell line D425 Med. Intracranially injected tumors were further characterized by bulk and single-cell RNA-sequencing. Resultslnc-HLX-2-7 is highly upregulated in group 3 MB cell lines, patient-derived xenografts, and primary MBs compared to other MB sub-groups as assessed by qRT-PCR, RNA-seq, and RNA fluorescence in situ hybridization (FISH). Depletion of lnc-HLX-2-7 with antisense oligonucleotides or CRISPR/Cas9 significantly reduced cell proliferation and 3D colony formation and induced apoptosis. lnc-HLX-2-7-deleted D425 Med cells injected into mouse cerebella produced smaller tumors than those derived from parental cells. Pathway analysis revealed that lnc-HLX2-7 modulated oxidative phosphorylation, mitochondrial dysfunction, and sirtuin signaling pathways. The MYC oncogene regulated lnc-HLX-2-7, and the small molecule BET-bromodomain (BRD4) inhibitor JQ1 reduced lnc-HLX2-7 expression. Conclusionslnc-HLX-2-7 is oncogenic in MB and represents a promising novel molecular marker and a potential therapeutic target in group 3 MBs in children. Key pointsO_LIlnc-HLX-2-7 is highly upregulated in group 3 medulloblastomas compared to other sub-groups. C_LIO_LIIn vitro and in vivo studies strongly support an oncogenic role for lnc-HLX2-7 in group 3 medulloblastoma. C_LIO_LIlnc-HLX-2-7 may be a novel biomarker and a potential therapeutic target in group 3 medulloblastoma. C_LI Importance of the studyGroup 3 medulloblastomas are associated with poor clinical outcomes, are difficult to subtype clinically, and their biology is poorly understood. In an effort to address these problems, we identified a group 3-specific long non-coding RNA, lnc-HLX-2-7, in an in silico analysis of 175 medulloblastomas and confirmed its expression in group 3 medulloblastoma cell lines, patient-derived xenografts, and FFPE samples. CRISPR/Cas9 deletion and antisense oligonucleotide knockdown of lnc-HLX-2-7 significantly reduced cell growth and 3D colony formation and induced apoptosis. Deletion of lnc-HLX-2-7 in cells injected into mouse cerebellums reduced tumor growth compared to parental cells, and RNA sequencing of these tumors revealed lnc-HLX-2-7-associated modulation of cell viability and cell death signaling pathways. The oncogene MYC regulates lnc-HLX-2-7, and its expression can be controlled by the BET-bromodomain (BRD4) inhibitor JQ1. lnc-HLX-2-7 is a candidate biomarker and a potential therapeutic target in group 3 medulloblastomas in children.

cancer biology↗

bioRxiv2020

In situ measurement of intracellular thermal conductivity using heater-thermometer hybrid diamond nanosensor

Understanding heat dissipation processes at nanoscale during cellular thermogenesis is essential to clarify the relationships between the heat and biological processes in cells and organisms. A key parameter determining the heat flux inside a cell is the local thermal conductivity, a factor poorly investigated both experimentally and theoretically. Here, using a nanoheater/nanothermometer hybrid based on a polydopamine shell encapsulating a fluorescent diamond nanocrystal, we measured the intracellular thermal conductivity of HeLa cell with a spatial resolution of about 200 nm. Its mean value of 0.11 Wm-1K-1 determined for the first time is significantly smaller than that of water. Bayesian analysis of the data strongly supports the existence of variation of the intracellular thermal conductivity of about 40%. These results present a major milestone towards understanding the intracellular heat transfer phenomena at nanoscale.

cell biology↗

bioRxiv2020

Systematic Discovery of Salmonella Phage-Host Interactions via High-Throughput Genome-Wide Screens

Though bacteriophages (phages) are known to play a crucial role in bacterial fitness and virulence, our knowledge about the genetic basis of their interaction, cross-resistance and host-range is sparse. Here, we employed genome-wide screens in Salmonella enterica serovar Typhimurium to discover host determinants involved in resistance to eleven diverse lytic phages including 4 new phages isolated from a therapeutic phage cocktail. We uncovered 301 diverse host factors essential in phage infection, many of which are shared between multiple phages demonstrating potential cross-resistance mechanisms. We validate many of these novel findings and uncover the intricate interplay between RpoS, the virulence-associated general stress response sigma factor and RpoN, the nitrogen starvation sigma factor in phage cross-resistance. Finally, the infectivity pattern of eleven phages across a panel of 23 genome sequenced Salmonella strains indicates that additional constraints and interactions beyond the host factors uncovered here define the phage host range.

microbiology↗

bioRxiv2020

Generation of multi-transgenic pigs using PiggyBac transposons co-expressing pectinase, xylanase, cellulase?β-1.3-1.4-glucanase and phytase

The current challenges facing the pork industry are to maximize feed efficiency and minimize fecal emissions. Unlike ruminants, pigs lack a number of digestive enzymes like pectinase, xylanase, cellulase, {beta}-1.3-1.4-glucanase and phytase to hydrolyze the cell walls of grains to release endocellular nutrients into their digestive tracts. Herein, we synthesized multiple cellulase and pectinase genes derived from lower organisms and then codon optimized these genes to be expressed in pigs. These genes were then cloned into our previously optimized XynB (xylanase)- EsAPPA (phytase) bicistronic construct. We then successfully generated transgenic pigs that expressed four enzymes (Pg7fn (pectinase), XynB (xylanase), EsAPPA (phytase) and TeEGI (cellulase and {beta}-glucanase)) using somatic cell cloning. Expression of these genes was parotid gland specific. Enzymatic assays using the saliva of these founders demonstrated high levels of phytase (2.0~3.4 U/mL) and xylanase (0.25~0.42 U/mL) activity, but low levels of pectinase (0.06~0.08 U/mL) activity. These multi-transgenic pigs are expected to contribute to enhance feed utilization and reduce environmental impact.

genetics↗

bioRxiv2020

High-throughput mapping of the phage resistance landscape in E. coli

Bacteriophages (phages) are critical players in the dynamics and function of microbial communities and drive processes as diverse as global biogeochemical cycles and human health. Phages tend to be predators finely tuned to attack specific hosts, even down to the strain level, which in turn defend themselves using an array of mechanisms. However, to date, efforts to rapidly and comprehensively identify bacterial host factors important in phage infection and resistance have yet to be fully realized. Here, we globally map the host genetic determinants involved in resistance to 14 phylogenetically diverse double-stranded DNA phages using two model Escherichia coli strains (K-12 and BL21) with known sequence divergence to demonstrate strain-specific differences. Using genome-wide loss-of-function and gain-of-function genetic technologies, we are able to confirm previously described phage receptors as well as uncover a number of previously unknown host factors that confer resistance to one or more of these phages. We uncover differences in resistance factors that strongly align with the susceptibility of K-12 and BL21 to specific phage. We also identify both phage specific mechanisms, such as the unexpected role of cyclic-di-GMP in host sensitivity to phage N4, and more generic defenses, such as the overproduction of colanic acid capsular polysaccharide that defends against a wide array of phages. Our results indicate that host responses to phages can occur via diverse cellular mechanisms. Our systematic and high-throughput genetic workflow to characterize phage-host interaction determinants can be extended to diverse bacteria to generate datasets that allow predictive models of how phage-mediated selection will shape bacterial phenotype and evolution. The results of this study and future efforts to map the phage resistance landscape will lead to new insights into the coevolution of hosts and their phage, which can ultimately be used to design better phage therapeutic treatments and tools for precision microbiome engineering.

microbiology↗

bioRxiv2019

Tet2 negatively regulates memory fidelity

Despite being fully differentiated, DNA methylation is dynamically regulated in post-mitotic glutamatergic neurons in the CA1 of the hippocampus through competing active DNA methylation and de-methylation, a process that regulates neuronal plasticity. Active DNA methylation after learning is necessary for long-term memory formation, and active DNA de-methylation by the TET enzymes has been implicated as a counter-regulator of that biochemical process. We demonstrate that Tet2 functions in the CA1 as a negative regulator of long-term memory, whereby its knockdown across the CA1 or haploinsufficiency in glutamatergic neurons enhances the fidelity of hippocampal-dependent spatial and associative memory. Loci of altered DNA methylation were then determined using whole genome bisulfite sequencing from glutamatergic Tet2 haploinsufficient CA1 tissue, which revealed hypermethylation in the promoters of genes known to be transcriptionally regulated after experiential learning. This study demonstrates a link between Tet2 activity at genes important for memory formation in CA1 glutamatergic neurons and memory fidelity.

neuroscience↗

bioRxiv2019

A novel microRNA-based strategy to expand the differentiation potency of stem cells

Full differentiation potential along with self-renewal capacity is a major property of pluripotent stem cells (PSCs). However, the differentiation capacity frequently decreases during expansion of PSCs in vitro. We show here that transient exposure to a single microRNA, expressed at early stages during normal development, improves the differentiation capacity of already-established murine and human PSCs. Short exposure to miR-203 in PSCs (miPSCs) results in expanded differentiation potency as well as improved efficiency in stringent assays such as tetraploid complementation and human-mouse interspecies chimerism. Mechanistically, these effects are mediated by direct repression of de novo DNA methyltransferases Dnmt3a and Dnmt3b, leading to transient and reversible erasing of DNA methylation. As a proof of concept, miR-203 improves differentiation and maturation of PSCs into cardiomyocytes in vitro as well as cardiac regeneration in vivo, after cardiac injury. These data support the use of transient exposure to miR-203 as a general and single method to reset the epigenetic memory in PSCs, and improve their use in regenerative medicine.

cell biology↗

bioRxiv2019

Hsa_circ_0001947 suppresses acute myeloid leukemia progression by sponging hsa-miR-329-5p and regulating CREBRF expression

Acute myeloid leukemia (AML) is a heterogeneous group of diseases resulting from clonal transformation of hematopoietic precursors through the acquisition of chromosomal rearrangements and multiple gene mutations. Accumulating evidence has indicated that aberrantly expressed circular RNAs (circRNAs) are involved in cancer development and progression. However, their clinical values and biological roles in AML remain unclear. In this study, we identified the aberrantly down-regulated profile of hsa_circ_0001947 in AML through microarray analysis and validated it with quantitative reverse transcription polymerase chain reaction (qRT-PCR). Then, we explored the clinical significance, biological functions and regulatory mechanisms of hsa_circ_0001947 in AML patients. The results showed that lower hsa_circ_0001947 expression was positively correlated with higher leukemia cells in bone marrow or peripheral blood, indicating poor prognosis. Further, bioinformatics analysis demonstrated hsa_circ_0001947-hsa-miR-329-5p-CREBRF network. Down-regulation of hsa_circ_0001947 by siRNA promoted cell proliferation, inhibited apoptosis, reduced drug resistance of AML cells, and also decreased the expression of its targeted gene, CREBRF. The mimics of hsa-miR-329-5p reduced drug resistance and decreased the expression of CREBRF, while its inhibitor manifested anti-leukemia effects and increased CREBRF expression. In vivo studies revealed that silencing hsa_circ_0001947 promoted the tumor growth in BALB/c nude mice. Collectively, our findings suggest that hsa_circ_0001947 functions as a tumor inhibitor to suppress AML cell proliferation through hsa-miR-329-5p/CREBRF axis, which would be a novel target for AML therapy.

cancer biology↗