Biology subjects

Xu, X.

Publications and source records attributed to Xu, X..

At least 487 records · Page 27Linked to original sources

bioRxiv2022

Small silencing RNAs expressed from W-linked retrocopies of Masculinizer target the male-determining gene PxyMasc during female sex determination in the Diamondback moth Plutella xylostella

The Lepidoptera are an insect order of cultural, economic and environmental importance, representing c. 10% of all described living species. Yet, for all but one of these species (silkmoth, Bombyx mori) the molecular genetics of how sexual fate is determined remains unknown. We investigated this in the diamondback moth (DBM - Plutella xylostella), a globally important, highly invasive and economically damaging pest of cruciferous crops. Our previous work uncovered a regulator of male sex determination in DBM - PxyMasc, a homologue of B. mori Masculinizer - which although initially expressed in embryos of both sexes, is then reduced in female embryos, leading to female-specific splicing of doublesex. Here, through sequencing small RNA libraries generated from early embryos and sexed larval pools, we identified a variety of small silencing RNAs (predominantly piRNAs) complementary to PxyMasc, whose temporal expression correlated with the reduction in PxyMasc transcript observed previously in females. Analysis of these small RNAs showed that they are expressed from tandemly-arranged, multi-copy arrays found exclusively on the W (female-specific) chromosome, which we term Pxyfem. Analysis of the Pxyfem sequences showed that they are partial cDNAs of PxyMasc mRNA transcripts, likely integrated into transposable element graveyards by the non-canonical action of retrotransposons (retrocopies), and that their apparent similarity to B. mori feminizer more probably represents convergent evolution. Our study helps elucidate the sex determination cascade in this globally important pest and highlights the shortcuts which retrotransposition events can facilitate in the evolution of complex molecular cascades, including sex determination. Significance statementUncovering the mechanisms which species have evolved to determine sex is of fundamental interest and provides avenues for pest management through genetic manipulation of these pathways. In insects, much of what is known regarding sex determination is concentrated within the Diptera and Hymenoptera, despite other orders (e.g. Lepidoptera) being of great ecological and economic importance. Here, using small RNA sequencing of embryonic and early larval samples, we uncover an RNAi-based sex determination system which silences the male determining gene PxyMasc in the Diamondback moth (Plutella xylostella) - a global pest of cruciferous crops. We track production of these silencing RNAs back to the W-chromosome where they are expressed from partial cDNA copies of PxyMasc. Our analysis suggests these are PxyMasc retrocopies, integrated via the non-canonical action of LTR retrotransposons and that similarities between this system and the feminizer system in Bombyx mori likely represent convergent evolution.

developmental biology↗

bioRxiv2022

Genomic insights into present local adaptation and future climate change vulnerability of a keystone forest tree species in East Asian

Rapid global climate change is posing a huge threat to biodiversity. Assessments of the adaptive capacity for most taxa is usually performed on the species as a whole, but fails to incorporate intraspecific adaptive variation that may play a fundamental role in buffering future shifting climates. Here we generate a chromosome-scale genome assembly for Populus koreana, a pioneer and keystone tree species in East Asia temperate forests. We also obtain whole-genome sequences of 230 individuals collected from 24 natural populations. An integration of population genomics and environmental variables was performed to reveal the genomic basis of local adaptation to diverse climate variable. We identify a set of climate-associated single nucleotide polymorphisms (SNPs), insertions-deletions (Indels) and structural variations (SVs), in particular numerous adaptive non-coding variants distributed across the genome of P. koreana. We incorporate these variants into an environmental modelling scheme to predict spatiotemporal responses of P. koreana to future climate change. Our results highlight the insights that the integration of genomic and climate data can shed on the future evolutionary adaptive capacities of a species to changing environmental conditions.

evolutionary biology↗

bioRxiv2022

Biological responses to terahertz radiation with different power density in primary hippocampal neurons

BackgroundTerahertz (THz) radiation is a valuable imaging and sensing tool which is widely used in industry and medicine. However, it biological effects including genotoxicity and cytotoxicity are not clear, particularly on the nervous system. In this study, we investigated how THz radiation with different frequency and intensity would affect the morphology, cell growth and function of rat hippocampal neurons in vitro. MethodsPrimary hippocampal neuronal cells were isolated from newborn Wistar rat pups and were exposed to THz radiation with the frequencies of 0.12 THz and 0.141 THz, at an power intensities of 10 mW/cm2 and 30 mW/cm2 respectively. The cellular activities were evaluated by Cell Counting Kit-8 after exposure for 10 min and 30 min. The cellular apoptosis was examined by Annexin V staining using flow cytometry and the ultrastructure was detected by electron microscopy. Moreover, the amount of amino acid in the cultured neurons was measured by high performance liquid chromatography (HPLC). ResultsNo obvious morphological changes, such as axon length and axon number, could be detected in primary neurons after exposure to 10mW/cm2 or 50 mW/cm2 THz for 30 min. However, the overall cellular activities were differentially affected by 10mW/cm2 and 50 mW/cm2 THz. Obvious cellular apoptosis was induced by both 10mW/cm2 and 50 mW/cm2 exposure. We also found that the amounts of most amino acids did not change significantly after exposure to these two types of THz radiation. ConclusionsThe effects of THz radiation on hippocampal neurons depend on frequency, power, exposure time as well as the measurement time after the exposure. These results will provide important information for further investigation of the effect of THz radiation on the nervous system.

neuroscience↗

bioRxiv2022

Sperm mosaicism predicts transmission of de novo mutations to human blastocysts

De novo mutations underlie individually rare but collectively common pediatric congenital disorders. Some of these mutations can also be detected in tissues and from cells in a parent, where their abundance and tissue distribution can be measured. We previously reported that a subset of these mutations is detectable in sperm from the father, predicted to impact the health of offspring. Here, in three independent couples undergoing in vitro fertilization, we first assessed male gonadal mosaicism, then assessed the transmission of the mutations to their preimplantation blastocysts. We found an overall predictable transmission but slight under-transmission of mutations to blastocysts based upon measured mutational abundance in sperm, and we replicated this conclusion in an independent family-based cohort. Therefore, unbiased preimplantation genetic testing for gonadal mosaicism may represent a feasible approach to reduce the transmission of potentially harmful de novo mutations, which could help to reduce their impact on miscarriage and pediatric disease.

genetics↗

bioRxiv2022

Development of visual cortex in human neonates are selectively modified by postnatal experience

Experience-dependent cortical plasticity is a pivotal process of human brain development and essential for the formation of most cognitive functions. Although studies found that early visual experience could influence the endogenous development of visual cortex in animals, little is known about such impact on human infants. Using the multi-modal MRI data from developing human connectome project, we revealed the early structural and functional maps in the ventral visual cortex and their development across the first month of age. Particularly, we found the postnatal experience could modulate both the cortical morphology in ventral visual cortex and the functional circuit between bilateral primary visual cortices. But the cortical myelination and overall functional circuits of ventral cortex, particularly that of the high-order visual cortex, developed without significant influence of postnatal experience in such early period. These experience-dependent cortical properties were further validated in the preterm-born infants who have longer postnatal time but immature cortical development at birth. The results confirmed that the development of cortical thickness was dominated by the postnatal experience but the functional circuit might be determined by the overall maturity of visual cortex. These data suggest in human newborns that early postnatal experience shapes the structural and functional development of the visual cortex in selective and organized pattern.

neuroscience↗

bioRxiv2022

STOmicsDB: a database of Spatial Transcriptomic data

Recent technological development in spatial transcriptomics allows researchers to measure gene expression of cells and their spatial locations at the almost single-cell level, which generates detailed biological insight into biological processes. However, specialized spatial transcriptomics databases are rare. Here, we present the Spatial TranscriptOmics DataBase (STOmicsDB), a user-friendly database with multifunctions including search of relevant publications and tools, public dataset visualization, customized specialized databases, new data archive, and online analysis. The current version of STOmicsDB consists of 141 curated spatial transcript datasets covering 12 species, and includes 5,618 spatial multi-omics publications and 674 tools. STOmicsDB is freely accessible at https://db.cngb.org/stomics/.

genomics↗

bioRxiv2022

Longitudinal dynamics of microvascular recovery after acquired cortical injury

Acquired brain injuries due to trauma damage cortical vasculature, which in turn impairs blood flow to injured tissues. There are reports of vascular morphological recovery following traumatic brain injury (TBI), but the remodeling process has not been examined longitudinally in detail after injury in vivo. Understanding the dynamic processes that influence recovery is thus critically important. We evaluated the longitudinal and dynamic microvascular recovery and remodeling up to 2 months post injury using live brain miniscope and 2-photon microscopic imaging. The new imaging approaches captured dynamic morphological and functional recovery processes at high spatial and temporal resolution in vivo. Vessel painting documented the initial loss and subsequent temporal morphological vascular recovery at the injury site. Miniscopes were used to longitudinally image the temporal dynamics of vascular repair in vivo after brain injury in individual mice across each cohort. We observe near-immediate nascent growth of new vessels in and adjacent to the injury site that peaks between 14-21 days post injury. 2-photon microscopy confirms new vascular growth and further demonstrates differences between cortical layers after cortical injury: large vessels persist in deeper cortical layers (>200 m), while superficial layers exhibit a dense plexus of fine (and often non-perfused) vessels displaying regrowth. Functionally, blood flow increases mirror increasing vascular density. Filopodia development and endothelial sprouting is measurable within 3 days post injury that rapidly transforms regions devoid of vessels to dense vascular plexus in which new vessels become increasingly perfused. Within 7 days post injury, blood flow is observed in these nascent vessels. Behavioral analysis reveals improved vascular modulation after 9 days post injury, consistent with vascular regrowth. We conclude that morphological recovery events are closely linked to functional recovery of blood flow to the compromised tissues, which subsequently leads to improved behavioral outcomes.

neuroscience↗

bioRxiv2022

Rational evolution of a recombinant DNA polymerase for efficient incorporation of unnatural nucleotides by dual-site boosting

Machine learning modelling assisting function-oriented enzyme engineering is normally built on predefined protein sequence space. However, efficient defining the determinant amino acid positions upon which the combinatorial mutation library is constructed is still a challenge in protein science. Herein, we present a comprehensive investigation of modifying a recombinant DNA polymerase for efficient incorporating one unnatural nucleotide, including the identification of key sites/regions, machine learning-assisted mutants screening, and the underlying mechanism of kinetics boosting. By using hundreds of training points and only dozens of testing samples, we found that one highly engineered enzymes catalytic efficiency can be further improved by one order of magnitude by specific mutation on two sites, 485I and 451L. Compared to the position 485 which is known to dominate local conformation of B-family DNA polymerases, 451 is a split-new active site discovered by our approach. A novel allosteric regulation mechanism is underlying the apparent synergy of 485I and 451L on the kinetics boosting. As a result, a "half-closed" conformation of the binding pocket and a cooperative binding of both primer and template DNA strands on the protein accelerated the processes of substrates incorporation, molecular recognition, and releasing of incorrect nucleotides. These findings have implications in guiding the function-tuning of DNA polymerases for a broad range of biotechnological applications.

biochemistry↗

bioRxiv2022

A novel missense mutation in the proprotein convertase gene furinb causes hepatic cystogenesis during liver development in zebrafish

Hepatic cysts are fluid-filled lesions in the liver that are estimated to occur in 5% of the population. They may cause hepatomegaly and abdominal pain. Progression to secondary fibrosis, cirrhosis, or cholangiocarcinoma can lead to morbidity and mortality. Previous studies of patients and rodent models have associated hepatic cyst formation with increased proliferation and fluid secretion in cholangiocytes, which are partially due to impaired primary cilia. Congenital hepatic cysts are thought to originate from faulty bile duct development, but the underlying mechanisms are not fully understood. In a forward genetic screen, we identified a zebrafish mutant that develops hepatic cysts during larval stages. Cyst formation in these mutants is not due to changes in biliary cell proliferation, bile secretion, or impairment of primary cilia. Instead, time-lapse live imaging data showed that the mutant biliary cells failed to form interconnecting bile ducts because of defects in motility and protrusive activity. Accordingly, immunostaining revealed an excessive and disorganized actin and microtubule cytoskeleton in the mutant biliary cells. By whole-genome sequencing, we determined that the cystic phenotype in the mutant was caused by a missense mutation in the furinb gene which encodes a proprotein convertase. The mutation alters Furinb localization and causes endoplasmic reticulum (ER) stress. The cystic phenotype could be suppressed by treatment with the ER stress inhibitor 4-phenylbutyric acid and exacerbated by treatment with the ER stress inducer tunicamycin. The mutant livers also exhibited increased mTOR signaling and treatment with the mTOR inhibitor rapamycin partially blocked cyst formation by reducing ER stress. Our study has established a novel vertebrate model for studying hepatic cystogenesis and illustrated the role of ER stress in the disease pathogenesis.

developmental biology↗

bioRxiv2022

Functional stemness-related genes revealed by single-cell profiling of naïve and stimulated human CD34+ cells from CB and mPB

Hematopoietic stem cells (HSCs) from different sources show varied repopulating capacity, and HSCs lose their stemness after long-time ex vivo culture. However, the underlying mechanisms of the stemness differences because of the cell sources and the culture stimulation are not fully understood. Here, we applied single-cell RNA-seq (scRNA-seq) to analyze the naive and stimulated human CD34+ cells from cord blood (CB) and mobilized peripheral blood (mPB). We collected over 16,000 single-cell data to construct a comprehensive trajectory inference map and characterized the HSCs population on the hierarchy top, which is under quiescent state. Then we compared HSCs in CB to those in mPB and HSCs of naive samples to those of cultured samples, and identified stemness-related genes (SRGs) associated with culture time (CT-SRGs) and cell source (CS-SRGs), respectively. Interestingly, CT-SRGs and CS-SRGs share genes enriched in the signaling pathways such as mRNA catabolic process, Translational initiation, Ribonucleoprotein complex biogenesis and Cotranslational protein targeting to membrane, suggesting dynamic protein translation and processing may be a common requirement for stemness maintenance. Meanwhile, CT-SRGs are enriched in pathways involved in glucocorticoid and corticosteroid response that affect HSCs homing and engraftment. In contrast, CS-SRGs specifically contain genes related purine and ATP metabolic process which is important to initiate hematopoiesis. Finally, we presented an application through a small-scale drug screening using Connectivity Map (CMap) against CT-SRGs and found a small molecule cucurbitacin I, targeting STAT3/JAK2, can efficiently expand HSCs ex vivo while maintaining its stemness. These results indicate SRGs revealed by scRNA-seq can provide helpful insights to understand the stemness differences under diverse circumstances, and CT-SRGs can be a valuable database to identify candidates enhancing functional HSCs expansion during ex vivo culture.

cell biology↗

bioRxiv2022

Sequential increase of PHGDH expression with Alzheimer's pathology and symptoms

We report consistent increases in phosphoglycerate dehydrogenase (PHGDH) expression in mouse models of Alzheimers disease (AD) (3xTg-AD) and related tauopathy (PS19), particularly in hippocampal astrocytes. Human single-cell RNA-sequencing data reveal a sequential increase of PHGDH expression in people with no, early, and late AD pathology, which is corroborated by protein mass spectrometry and immunohistochemical analyses of three independent cohorts. A sequential increase of PHGDH expression also correlates with increasing clinical AD symptoms and worsening cognitive decline in patients. The consistent increase of PHGDH expression in six AD cohorts (Mayo, ROSMAP, Mount Sinai, Baltimore, Amsterdam, and UCSD/UCI) corroborates with the recent report of PHGDH extracellular RNA in blood plasma as a candidate biomarker for early diagnosis of AD and offers a caution to the suggested use of L-serine as a potential therapy of AD.

neuroscience↗

bioRxiv2022

Single-cell analysis reveals a pathogenic cellular module associated with early allograft dysfunction after liver transplantation

Liver transplantation (LT) is the standard therapy for patients with end-stage liver disease. Although LT technology has markedly progressed in recent decades, early allograft dysfunction (EAD) exacerbates the current organ shortage and impacts the prognosis of recipients. However, understanding of cellular characteristics and molecular events contributing to EAD is limited. Here, a large single-cell transcriptomic atlas of transplanted livers collected from four patients is constructed, including 58,243 cells, which are classified into 14 cell types and 29 corresponding subtypes with known markers, including liver parenchymal cells and non-parenchymal cells with different cell states. Compared to the pre-LT livers, graft remodeling is noted in the post-LT livers, with marked changes in several immune cells in either cell ratios or cell states. More importantly, an EAD-associated pathogenic cellular module is identified, consisting of mucosal-associated invariant T (MAIT) cells, granzyme B (GZMB)+ granzyme K (GZMK)+ natural killer (NK) cells, and S100A12+ neutrophils, all of which are elevated in EAD patient after LT. This cellular module is also verified in two independent datasets. Collectively, these results reveal the cellular characteristics of transplanted livers and the EAD-associated pathogenic cellular module at the single-cell level, offering new insights into the EAD occurrence after LT.

genomics↗

bioRxiv2022

Preclinical Pharmacokinetics and In Vitro Properties of GS-441524, A Potential Oral Drug Candidate for COVID-19 Treatment

Preclinical pharmacokinetics (PK) and in vitro ADME properties of GS-441524, a potential oral agent for the treatment of Covid-19, were studied. GS-441524 was stable in vitro in liver microsomes, cytosols, and hepatocytes of mice, rats, monkeys, dogs, and humans. The plasma free fractions of GS-441524 were 62-78% across all studied species. The in vitro transporter study results showed that GS-441524 was a substrate of MDR1, BCRP, CNT3, ENT1, and ENT2; but not a substrate of CNT1, CNT2, and ENT4. GS-441524 had a low to moderate plasma clearance (CLp), ranging from 4.1 mL/min/kg in dogs to 26 mL/min/kg in mice; the steady state volume distribution (Vdss) ranged from 0.9 L/kg in dogs to 2.2 L/kg in mice after IV administration. Urinary excretion appeared to be the major elimination process for GS-441524. Following oral administration, the oral bioavailability was 8.3% in monkeys, 33% in rats, 39% in mice, and 85% in dogs. The PK and ADME properties of GS-441524 support its further development as an oral drug candidate.

pharmacology and toxicology↗

bioRxiv2022

An allosteric agonist activates BK channels by perturbing coupling between Ca2+ binding and pore opening

BK type Ca2+-activated K+ channels activate in response to both the membrane voltage and intracellular Ca2+ with distinct mechanisms. Ca2+ binds to the cytosolic domain (CTD) to open the pore across the membrane, but the mechanism that couples Ca2+ binding to pore opening is not clear. Here we show that a compound, BC5, identified using in silico screening, interacts with BK channels at the interface between the CTD and the transmembrane voltage sensing domain (VSD) and enhances channel activity by specifically affecting the Ca2+ dependent mechanism. BC5 activates the channel in the absence of Ca2+ binding but Ca2+ binding inhibits BC5 effects. Thus, BC5 perturbs the pathway that couples Ca2+ binding to pore opening to allosterically affect both, which is supported by atomistic simulations and mutagensis. The results suggest that the CTD- VSD interaction makes a major contribution to the mechanism of Ca2+ dependent activation and is an important site for allosteric agonists to modulate BK channel activation.

biophysics↗

bioRxiv2022

An optimized method for the isolation of urinary extracellular vesicles for molecular phenotyping: detection of biomarkers for radiation exposure

BackgroundUrinary extracellular vesicles (EVs) are a source of biomarkers with broad potential applications across clinical research, including monitoring radiation exposure. A key limitation to their implementation is minimal standardization in EV isolation and analytical analysis methods. Further, most urinary EV isolation protocols necessitate large volumes of sample. This study aimed to compare and optimize isolation and analytical methods for EVs from small volumes of urine. Methods3 EV isolation methods were compared: ultracentrifugation, magnetic bead-based, and size-exclusion chromatography from 0.5 mL or 1 mL of rat and human urine. EV yield and mass spectrometry signals (Q-ToF and Triple Quad) were evaluated from each method. Metabolomic profiling was performed on EVs isolated from the urine of rats exposed to ionizing radiation 1-, 14-, 30- or 90-days post-exposure, and human urine from patients receiving thoracic radiotherapy for the treatment of lung cancer pre- and post-treatment. ResultsSize-exclusion chromatography is the preferred method for EV isolation from 0.5 mL of urine. Mass spectrometry-based metabolomic analyses of EV cargo identified biochemical changes induced by radiation, including altered nucleotide, folate, and lipid metabolism. We have provided standard operating procedures for implementation of these methods in other laboratories. ConclusionsWe demonstrate that EVs can be isolated from small volumes of urine and analytically investigated for their biochemical contents to detect radiation induced metabolomic changes. These findings lay a groundwork to develop future methods to monitor response to radiotherapy and can be extended to an array of molecular phenotyping studies aimed at characterizing EV cargo.

cancer biology↗

bioRxiv2022

Computed tomographic analysis of the dental system of three Jurassic ceratopsians: implications for the evolution of the tooth replacement pattern and diet in early-diverging ceratopsians

The dental system of ceratopsids is among the most specialized structure in Dinosauria, and includes high angled wear surfaces, split tooth roots, and multiple teeth in each tooth family. However, the early evolution of this unique dental system is generally poorly understood due to a lack of knowledge of the dental morphology and development in early-diverging ceratopsians. Here we study the dental system of three of the earliest-diverging Chinese ceratopsians: Yinlong and Hualianceratops from the early Late Jurassic of Xinjiang, and Chaoyangsaurus from the Late Jurassic of Liaoning. By using micro-computed tomographic analyses, our study has revealed significant new information regarding the dental system of these early ceratopsians, including no more than five replacement teeth in each jaw quadrant; at most one generation of replacement teeth in each alveolus; nearly full resorption of the functional tooth root during tooth replacement; and occlusion with low-angled, concave wear facets that differs significantly from the shearing occlusal system seen in ceratopsids. Yinlong displays an increase in the number of maxillary tooth alveoli and a decrease in the number of replacement teeth during ontogeny as well as the retention of remnants of functional teeth in the largest individual. Early-diverging ceratopsians thus display a relatively slow tooth replacement rate compared to late-diverging ceratopsians. Combined with paleobotany and palaeoenvironment data, Yinlong likely uses gastroliths to triturate foodstuffs, and the difference in diet strategy might have influenced the pattern of tooth replacement in later-diverging ceratopsians.

paleontology↗

bioRxiv2022

Genome-wide SNPs of vegetable leafminer, Liriomyza sativae: insights into the recent Australian invasion

Liriomyza sativae, the vegetable leafminer, is a serious agricultural pest originally from the Americas which has now colonized all continents except Antarctica. In 2015, L. sativae arrived on the Australian mainland and established on the Cape York Peninsula in the northeast of the country. Here, we assessed genetic variation in L. sativae based on genome-wide single nucleotide polymorphisms (SNPs) generated by double-digest restriction-site associated DNA sequencing (ddRAD-seq) to uncover the potential origin(s) of this pest in Australia and contribute to reconstructing its global invasion history. Our principal component analyses (PCA) results suggested that Australian mainland populations were genetically close to populations from the Torres Strait and had connections to Bali and Papua New Guinea (PNG), whereas populations from Asia and Africa were more distantly related. Hawaii was genetically distinct from populations from Asia, Africa and Australia. Co-ancestry analyses pointed to signals of gene flow from the Torres Strait into the Australian mainland, while Indonesia/PNG were the likely sources of the initial invasion into the Torres Strait. Admixture analyses further revealed that L. sativae from the Torres Strait had genetic diversity originating from multiple sources, which has now spread to the Australian mainland. The L. sativae lineages from Asia/Africa appear closely related and may share co-ancestry. Isolation by distance (IBD) was found at a broad global scale, but not within small regions, suggesting human-mediated factors contribute to the local spread of this pest. Overall, our findings highlight the challenges in quarantine measures aimed at restricting the distribution of this global pest.

bioinformatics↗

bioRxiv2022

HMGN5 escorts oncogenic STAT3 signaling by regulating chromatin landscape in tumorigenesis of breast cancer

Epigenetic alterations are widely linked with carcinogenesis, therefore becoming emerging therapeutic targets in the treatment of cancers, including breast cancer. HMGNs are nucleosome binding proteins, which regulate chromatin structures in a cell type- and disease-specific manner. However, the roles of HMGNs in the tumorigenesis of breast cancer are less known. In this study, we report that HMGNs are highly expressed in 3D-cultured breast cancer cells. HMGN5, a member of HMGNs, controls the proliferation, invasion and metastasis of breast cancer cells in vitro and in vivo. Clinically, HMGN5 is an unfavorable prognostic marker in patients. Mechanistically, HMGN5 is governed by active STAT3 transcriptionally and further escorts STAT3 to shape oncogenic chromatin landscape and transcriptional program. Lastly, we provide evidence that interference of HMGN5 by nanoparticle-packaged siRNA is potentially an effective approach in breast cancer treatment. Taken together, our findings reveal a novel feed-forward circuit between HMGN5 and STAT3 in promoting breast cancer tumorigenesis and suggest HMGN5 as a novel epigenetic therapeutic-target in STAT3- hyperactive breast cancer.

cancer biology↗