Biology subjects

Yang, Z.

Publications and source records attributed to Yang, Z..

At least 469 records · Page 26Linked to original sources

bioRxiv2021

Structures of the human cholecystokinin receptors in complex with agonists and antagonists

Cholecystokinin receptors, CCKAR and CCKBR, are important neuro-intestinal peptide hormone receptors and play a vital role in food intake and appetite regulation. Here we report three crystal structures of the human CCKAR in complex with different ligands, including one peptide agonist and two small-molecule antagonists, as well as two cryo-electron microscopy structures of CCKBR-gastrin in complex with Gi2 and Gq, respectively. These structures reveal the recognition pattern of different ligand types and the molecular basis of peptide selectivity in the cholecystokinin receptor family. By comparing receptor structures in different conformational states, a stepwise activation process of cholecystokinin receptors is proposed. Combined with pharmacological data, our results provide atomic details for differential ligand recognition and receptor activation mechanisms. These insights will facilitate the discovery of potential therapeutics targeting cholecystokinin receptors.

biophysics↗

bioRxiv2021

Compensatory changes in contralesional node strength, brain wide modularity and cross-modular functional interactions in a rat model of traumatic brain injury

Penetrating cortical impact injuries alter neuronal communication beyond the injury epicenter, across regions involved in affective, sensorimotor, and cognitive processing. Understanding how traumatic brain injury (TBI) reorganizes local and brain wide nodal functional interactions may provide valuable quantitative parameters for monitoring pathological progression and functional recovery. To this end, we investigated spontaneous fluctuations in the functional magnetic resonance imaging (fMRI) signal obtained at 11.1 Tesla in rats sustaining controlled cortical impact (CCI) and imaged at 2- and 30-days post-injury. Graph theory-based calculations were applied to weighted undirected matrices constructed from 12,879 pairwise correlations between fMRI signals from 162 regions. Our data indicate that on days 2 and 30 post-CCI there is a significant increase in connectivity strength in nodes located in contralesional cortical, thalamic, and basal forebrain areas. Rats imaged on day 2 post-injury had significantly greater network modularity than controls, with influential nodes (with high eigenvector centrality) contained within the contralesional module and participating less in cross-modular interactions. By day 30, modularity and cross-modular interactions recover, although a cluster of nodes with low strength and low eigenvector centrality remain in the ipsilateral cortex. Our results suggest that changes in node strength, modularity, eigenvector centrality, and participation coefficient track early and late TBI effects on brain functional connectivity. We propose that the observed compensatory functional connectivity reorganization in response to CCI may be unfavorable to brain wide communication in the early post-injury period.

neuroscience↗

bioRxiv2021

Vascular KATP channel structural dynamics reveal regulatory mechanism by Mg-nucleotides

Vascular tone is dependent on smooth muscle KATP channels comprising pore-forming Kir6.1 and regulatory SUR2B subunits, in which mutations cause Cantu syndrome. Unique among KATP isoforms, they lack spontaneous activity and require Mg-nucleotides for activation. Structural mechanisms underlying these properties are unknown. Here, we determined the first cryoEM structures of vascular KATP channels bound to inhibitory ATP and glibenclamide, which differ informatively from similarly determined pancreatic KATP channel isoform (Kir6.2/SUR1). Unlike SUR1, SUR2B subunits adopt distinct rotational "propeller" and "quatrefoil" geometries surrounding their Kir6.1 core. The previously unseen ED-rich linker connecting the two halves of the SUR-ABC core is observed in a quatrefoil-like conformation. MD simulations reveal MgADP-dependent dynamic tripartite interactions between this linker, SUR2B and Kir6.1. The structures captured implicate a progression of intermediate states between MgADP-free inactivated and MgADP-bound activated conformations wherein the ED-rich linker participates as mobile autoinhibitory domain, suggesting a conformational pathway toward KATP channel activation.

biochemistry↗

bioRxiv2021

The SCP4-STK35/PDIK1L complex is a dual phospho-catalytic signaling dependency in acute myeloid leukemia

Acute myeloid leukemia (AML) cells rely on phospho-signaling pathways to gain unlimited proliferation potential. Here, we used domain-focused CRISPR screening to identify the nuclear phosphatase SCP4 as a dependency in AML, yet this enzyme is dispensable in normal hematopoietic progenitor cells. Using CRISPR exon scanning and gene complementation assays, we show that the catalytic function of SCP4 is essential in AML. Through mass spectrometry analysis of affinity-purified complexes, we identify the kinase paralogs STK35 and PDIK1L as binding partners and substrates of the SCP4 phosphatase domain. We show that STK35 and PDIK1L function catalytically and redundantly in the same pathway as SCP4 to maintain AML proliferation and to support amino acid biosynthesis and transport. We provide evidence that SCP4 regulates STK35/PDIK1L through two distinct mechanisms: catalytic removal of inhibitory phosphorylation and by promoting kinase stability. Our findings reveal a phosphatase-kinase signaling complex that supports the pathogenesis of AML.

cancer biology↗

bioRxiv2021

Noise-Transfer2Clean: Denoising cryo-EM images based on noise modeling and transfer

MotivationCryo-electron microscopy (cryo-EM) is a widely-used technology for ultrastructure determination, which constructs the three-dimensional (3D) structures of protein and macromolecular complex from a set of two-dimensional (2D) micrographs. However, limited by the electron beam dose, the micrographs in cryo-EM generally suffer from extremely low signal-to-noise ratio (SNR), which hampers the efficiency and effectiveness of downstream analysis. Especially, the noise in cryo-EM is not simple additive or multiplicative noise whose statistical characteristics are quite different from the ones in natural image, extremely shackling the performance of conventional denoising methods. ResultsHere, we introduce the Noise-Transfer2Clean (NT2C), a denoising deep neural network (DNN) for cryo-EM to enhance image contrast and restore specimen signal, whose main idea is to improve the denoising performance by correctly discovering the noise model of cryo-EM images and transferring the statistical nature of noise into the denoiser. Especially, to cope with the complex noise model in cryo-EM, we design a contrast-guided noise and signal re-weighted algorithm to achieve clean-noisy data synthesis and data augmentation, making our method authentically achieve signal restoration based on noises true properties. To our knowledge, NT2C is the first denoising method that resolves the complex noise model in cryo-EM images. Comprehensive experimental results on simulated datasets and real datasets show that NT2C achieved a notable improvement in image denoising and specimen signal restoration, comparing with the state-of-art methods. A real-world case study shows that NT2C can improve the recognition rate on hard-to-identify particles by 19% in the particle picking task.

bioinformatics↗

bioRxiv2021

METTL9 regulates N1-histidine methylation of zinc transporters to promote tumor growth

Methyltransferase like 9 (Mettl9) is a member of the methyltransferase like protein family which is characterized by the presence of binding domains for S-adenosyl methionine, (SAM), a co-substrate for methylation reactions. Despite METTL9 is predicted to be a methyltransferase, its enzymatic activity, substrate specificities and biological functions are still poorly characterized. In this study, we revealed a tumor-promoting role for METTL9. We found that deletion of Mettl9 in tumor cells suppresses tumor growth and elicits potent anti-tumor immunity. Mechanistically, METTL9 is a N1-histidine methyltransferase which methylates the histidine residues of a x-His-x-His (xHxH) motif on the substrates. This motif is found extensively in zinc transporter families SLC39s and SLC30s, particularly in SLC39A7. Deletion of Mettl9 impairs cytoplasmic zinc homeostasis, resulting in an altered gene expression program with increased endoplasmic reticulum (ER) stress and reduced cell cycle. Mutation of key METTL9 catalyzed methylhistidine residues of SLC39A7 impairs cytoplasmic zinc homeostasis and affects cell growth as well. Notably, METTL9 expression is increased in some cancer types and its higher expression is associated with worse clinical outcomes, particularly in liver and pancreatic cancer. In summary, our work identified METTL9 as a potential new oncogene and its mediated methylation is of regulatory importance. Identifying selective and potent small-molecule inhibitors of METTL9 could thus represent novel therapeutic strategy for anti-proliferative cancer drugs.

cancer biology↗

bioRxiv2021

Multi-scale semi-supervised clustering of brain images: deriving disease subtypes

Disease heterogeneity is a significant obstacle to understanding pathological processes and delivering precision diagnostics and treatment. Clustering methods have gained popularity for stratifying patients into subpopulations (i.e., subtypes) of brain diseases using imaging data. However, unsupervised clustering approaches are often confounded by anatomical and functional variations not related to a disease or pathology of interest. Semi-supervised clustering techniques have been proposed to overcome this and, therefore, capture disease-specific patterns more effectively. An additional limitation of both unsupervised and semi-supervised conventional machine learning methods is that they typically model, learn and infer from data using a basis of feature sets pre-defined at a fixed anatomical or functional scale (e.g., atlas-based regions of interest). Herein we propose a novel method, "Multi-scAle heteroGeneity analysIs and Clustering" (MAGIC), to depict the multi-scale presentation of disease heterogeneity, which builds on a previously proposed semi-supervised clustering method, HYDRA. It derives multi-scale and clinically interpretable feature representations and exploits a double-cyclic optimization procedure to effectively drive identification of inter-scale-consistent disease subtypes. More importantly, to understand the conditions under which the clustering model can estimate true heterogeneity related to diseases, we conducted extensive and systematic semi-simulated experiments to evaluate the proposed method on a sizeable healthy control sample from the UK Biobank (N=4403). We then applied MAGIC to imaging data from Alzheimers disease (ADNI, N=1728) and schizophrenia (PHENOM, N=1166) patients to demonstrate its potential and challenges in dissecting the neuroanatomical heterogeneity of common brain diseases. Taken together, we aim to provide guidance regarding when such analyses can succeed or should be taken with caution. The code of the proposed method is publicly available at https://github.com/anbai106/MAGIC. HighlightsO_LIWe propose a novel multi-scale semi-supervised clustering method, termed MAGIC, to disentangle the heterogeneity of brain diseases. C_LIO_LIWe perform extensive semi-simulated experiments on large control samples (UK Biobank, N=4403) to precisely quantify performance under various conditions, including varying degrees of brain atrophy, different levels of heterogeneity, overlapping disease subtypes, class imbalance, and varying sample sizes. C_LIO_LIWe apply MAGIC to MCI and Alzheimers disease (ADNI, N=1728) and schizophrenia (PHENOM, N=1166) patients to dissect their neuroanatomical heterogeneity, providing guidance regarding the use of the semi-simulated experiments to validate the subtypes found in actual clinical applications. C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=166 SRC="FIGDIR/small/440501v2_ufig1.gif" ALT="Figure 1"> View larger version (48K): org.highwire.dtl.DTLVardef@2769e9org.highwire.dtl.DTLVardef@19a691borg.highwire.dtl.DTLVardef@6a9264org.highwire.dtl.DTLVardef@b0e686_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

bioRxiv2021

Reduced graphene oxide membrane as supporting film for high-resolution cryo-EM

Although single-particle cryogenic electron microscopy (cryo-EM) has been applied extensively for elucidating many crucial biological mechanisms at the molecular level, this technique still faces critical challenges, the major one of which is to prepare the high-quality cryo-EM specimen. Aiming to achieve a more reproducible and efficient cryo-EM specimen preparation, novel supporting films including graphene-based two-dimensional materials have been explored in recent years. Here we report a robust and simple method to fabricate EM grids coated with single- or few-layer reduced graphene oxide (RGO) membrane in large batch for high-resolution cryo-EM structural determination. The RGO membrane has decreased interlayer space and enhanced electrical conductivity in comparison to regular graphene oxide (GO) membrane. Moreover, we found that the RGO supporting film exhibited nice particle-absorption ability, thus avoiding the air-water interface problem. More importantly, we found that the RGO supporting film is particularly useful in cryo-EM reconstruction of sub-100 kDa biomolecules at near-atomic resolution, as exemplified by the study of RBD-ACE2 complex and other small protein molecules. We envision that the RGO membranes can be used as a robust graphene-based supporting film in cryo-EM specimen preparation.

biophysics↗

bioRxiv2021

Genome-wide mediation analysis: bridging the dividebetween genotype and phenotype via transcriptomicdata in maize

Mapping genotype to phenotype is an essential topic in genetics and genomics research. As the Omics data become increasingly available, genome-wide association study (GWAS) has been widely applied to establish the relationship between genotype and phenotype. However, signals detected by GWAS usually span broad genomic regions with many underneath candidate genes, making it challenging to interpret and validate the molecular functions of the candidate genes. Under the context of genetics research, we hypothesized a causal chain from genotype to phenotype partially mediated by intermediate molecular processes, i.e., gene expression. To test this hypothesis, we applied the high dimensional mediation analysis, a class of causal inference method with an assumed causal chain from the exposure to the mediator to the outcome, and implemented it to the maize diversity panel (N=280 lines). Using 40 publicly available agronomic traits, 66 newly generated metabolic traits, and published RNA-seq data from seven different tissues, we detected N=736 unique mediating genes, explaining an average of 12.7% phenotypic variance due to mediation. Noticeably, 83/736 (11%) genes were identified in mediating more than one trait, suggesting the prevalence of pleiotropic mediating effects. Among those pleiotropic mediators, benzox-azinone synthesis 13 (Bx13), a well-characterized gene encoding a 2-oxoglutarate-dependent dioxygenase, was identified mediating 40 agronomic and metabolic traits in different tissues. Further genetic and genomic analyses of the Bx13 and adjacent mediating genes suggested a 3D co-regulation modulation likely affect their expression levels and eventually lead to phenotypic consequences. Our results suggested the genome-wide mediation analysis is a powerful tool to integrate Omics data in providing causal inference to connect genotype to phenotype.

genetics↗

bioRxiv2021

Reconstructing genotypes from GWAS Summary Statistics

The emergence of genomewide association studies (GWAS) has led to the creation of large repositories of human genetic variation, creating enormous opportunities for genetic research and worldwide collaboration. Methods that are based on GWAS summary statistics seek to leverage such records, overcoming barriers that often exist in individual-level data access while also offering significant computational savings. Here, we propose a novel framework that can reconstruct allelic and genotypic counts/frequencies for each SNP from case-control GWAS summary statistics. Our framework is simple and efficient without the need of any complicated underlying assumptions. Illustrating the great potential of this framework we also propose three summary-statistics-based applications implemented in a new software package (ReACt): GWAS meta-analysis (with and without sample overlap), case-case GWAS, and, for the first time, group polygenic risk score (PRS) estimation. We evaluate our methods against the current state-of-the-art on both synthetic data and real genotype data and show high performance in power and error control. Our novel group PRS method based on summary statistics could not be achieved prior to our proposed framework. We demonstrate here the potential applications and advantages of this approach. Our work further highlights the great potential of summary-statistics-based methodologies towards elucidating the genetic background of complex disease and opens up new avenues for research.

genetics↗

bioRxiv2021

Phase Resolution of Heterozygous Sites in Diploid Genomes is Important to Phylogenomic Analysis under the Multispecies Coalescent Model

AO_SCPLOWBSTRACTC_SCPLOWGenome sequencing projects routinely generate haploid consensus sequences from diploid genomes, which are effectively chimeric sequences with the phase at heterozygous sites resolved at random. The impact of phasing errors on phylogenomic analyses under the multispecies coalescent (MSC) model is largely unknown. Here we conduct a computer simulation to evaluate the performance of four phase-resolution strategies (the true phase resolution, the diploid analytical integration algorithm which averages over all phase resolutions, computational phase resolution using the program PHASE, and random resolution) on estimation of the species tree and evolutionary parameters in analysis of multi-locus genomic data under the MSC model. We found that species tree estimation is robust to phasing errors when species divergences were much older than average coalescent times but may be affected by phasing errors when the species tree is shallow. Estimation of parameters under the MSC model with and without introgression is affected by phasing errors. In particular, random phase resolution causes serious overestimation of population sizes for modern species and biased estimation of cross-species introgression probability. In general the impact of phasing errors is greater when the mutation rate is higher, the data include more samples per species, and the species tree is shallower with recent divergences. Use of phased sequences inferred by the PHASE program produced small biases in parameter estimates. We analyze two real datasets, one of East Asian brown frogs and another of Rocky Mountains chipmunks, to demonstrate that heterozygote phase-resolution strategies have similar impacts on practical data analyses. We suggest that genome sequencing projects should produce unphased diploid genotype sequences if fully phased data are too challenging to generate, and avoid haploid consensus sequences, which have heterozygous sites phased at random. In case the analytical integration algorithm is computationally unfeasible, computational phasing prior to population genomic analyses is an acceptable alternative.

evolutionary biology↗

bioRxiv2021

The Detection of Bergeyella zoohelcum in Young Children after Cat Bite

Bergeyella zoohelcum is an uncommon zoonotic pathogen typically associated with cat or dog bites. Previously, only 14 cases of B. zoohelcum infection have been reported. We isolated the bacteria from the face of a 2-year-old girl who was bitten by a cat. The organism was identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and 16S rRNA gene sequence, and phylogenetic analysise supported that this isolate was belong to B. zoohelcum. Due to the contradicts of culture characteristics of B. zoohelcum which described in reported literatures, we used different media to culture the bacteria. After 24 h incubation, Colombia blood agar (CBA), Mueller-Hinton agar plate with 5% sheep blood and chocolate agar (CA) grew well, but blood agar (BA) grew well until 72 h. The strain did not grow on McConkey agar (MAC), Mueller-Hinton agar (MHA) and chocolate agar (containing vancomycin). The low detection rate of this strain was related to its harsh growth conditions and the limitations of traditional identification techniques. With the popularization of MALDI-TOF MS and 16S rRNA gene sequence and our further understanding of the fastidious bacteria, we will quickly and accurately identify the B. zoohelcum, meanwhile the detection rate of this bacterium will also be significantly improved. So that clinicians can achieve precise anti-infective treatment according to antimicrobial susceptibility testing.

microbiology↗

bioRxiv2021

Constructing phylogenetic relationship based on the independent selection law of genome sequences

Exploring the composition and evolution regularity of genome sequences and constructing phylogenetic relationship by alignment-free method in genome level are high-profile topics. Our previous researches discovered the CG and TA independent selection law s existed in genome sequences by analysis on the spectral features of 8-mer subsets of 920 eukaryote and prokaryote genomes. We found that the evolution state of genomes is determined by the intensity of the two independent selections and the degree of the mutual inhibition between them. In this study, the two independent selection patterns of 22 primate and 28 insect genome sequences were analyzed further. The two complete 8-mer motif sets containing CG or TA dinucleotide and their feature of relative frequency are proposed. We found that the two 8-mer sets and their feature are related directly to sequence evolution of genomes. According to the relative frequency of two 8-mer sets, phylogenetic trees were constructed respectively for the given primate and insect genomes. Through analysis and comparison, we found that our phylogenetic trees are more consistent with the known conclusions. The two kinds of phylogenetic relationships constructed by CG 8-mer set and TA 8-mer set are similar in insect genomes, but the phylogenetic relationship constructed by CG 8-mer set reflect the evolution state of genomes in current age and phylogenetic relationship constructed by TA 8-mer set reflect the evolution state of genomes in a slight earlier period. We thought it is the result that the TA independent selection is repressed by the CG independent selection in the process of genome evolution. Our study provides a theoretical approach to construct more objective evolution relationships in genome level.

evolutionary biology↗

bioRxiv2021

Mechano-transduction via the pectin-FERONIA complex regulates ROP6 GTPase signaling in Arabidopsis

During growth and morphogenesis, plant cells respond to mechanical stresses resulting from spatiotemporal changes in the cell wall that bear high internal turgor pressure. Microtubule (MT) arrays are re-organized to align in the direction of maximal tensile stress to guide the synthesis of cellulose, reinforcing the local cell wall. However, how mechanical forces regulate MT re-organization remains largely unknown. Here, we demonstrate that mechanical signaling that is based on the CrRLK1L subfamily receptor kinase FERONIA (FER) regulates the reorganization of cortical MT in cotyledon epidermal pavement cells (PC) in Arabidopsis. Recessive mutations in FER compromised MT response to mechanical perturbations such as single cell ablation, compression and Isoxaben treatment in these pavement cells. These perturbations promoted the activation of ROP6 GTPase that acts directly downstream of FER. Furthermore, defects in the ROP6 signaling pathway negated the reorganization of cortical MTs induced by these stresses. Finally, reduction in highly demethylesterified pectin, which binds the extracellular malectin domain of FER and is required for FER-mediated ROP6 activation, also impacted mechanical induction of cortical MT reorganization. Taken together our results suggest that the FER-pectin complex senses and/or transduce mechanical forces to regulate MT organization through activating the ROP6 signaling pathway in Arabidopsis.

cell biology↗

bioRxiv2021

Nonsense Mediated RNA Decay Is a Unique Vulnerability of Cancer Cells with SF3B1 and U2AF1 Mutations

Nonsense-mediated RNA decay (NMD) is well recognized as an RNA surveillance pathway that targets aberrant mRNAs with premature translation termination codons (PTCs) for degradation; however, its molecular mechanisms and roles in health and disease remain incompletely understood. In this study, we developed a novel reporter system that can accurately measure NMD activity in individual cells. By carrying out a genome-wide CRISPR/Cas9 knockout screen using this reporter system, we identified novel NMD-promoting factors, including multiple components of the SF3B complex and other U2 spliceosome factors. Interestingly, we also found that cells with mutations in the U2 spliceosome genes SF3B1 and U2AF1--which are commonly found in myelodysplastic syndrome (MDS) and cancers--have overall attenuated NMD activity. Furthermore, we found that compared to wild type cells, SF3B1 and U2AF1 mutant cells are more sensitive to NMD inhibition, a phenotype that is accompanied by elevated DNA replication obstruction, DNA damage and chromosomal instability. Remarkably, the sensitivity of spliceosome mutant cells to NMD inhibition could be rescued by overexpression of RNase H1, which removes R-loops in the genome. Together, our findings shed new light on the functional interplay between NMD and RNA splicing and suggest a novel strategy for the treatment of MDS and cancers with spliceosome mutations.

cell biology↗

bioRxiv2021

A malaria parasite phospholipid flippase safeguards midgut traversal of ookinetes for mosquito transmission

Mosquito midgut epithelium traversal is an essential component of transmission of malaria parasites. Phospholipid flippases are eukaryotic type IV ATPases (P4-ATPases), which in association with CDC50 cofactors, translocate phospholipids across lipid bilayers to maintain the membrane asymmetry. In this study, we investigated the function of a putative P4-ATPase, ATP7, from the rodent malaria parasite P. yoelii. Disruption of ATP7 results in block of parasite infection of mosquitoes. ATP7 is localized on the ookinete plasma membrane. While ATP7-depleted ookinetes are motile and capable of invading the midgut, they are quickly eliminated within the epithelial cells by a process that is independent from the mosquito complement-like immunity. ATP7 colocalizes and interacts with the flippase co-factor CDC50C. Importantly, depletion of CDC50C phenocopies ATP7 deficiency. ATP7-depleted ookinetes fail to translocate phosphatidylcholine (PC) across the plasma membrane, resulting in PC exposure at the ookinete surface. Lastly, ookinete microinjection into the mosquito hemocoel reverses the ATP7 deficiency phenotype. Our study identifies Plasmodium flippase as a novel mechanism of parasite survival in the midgut epithelium that is required for mosquito transmission.

microbiology↗

bioRxiv2021

TCR signaling promotes the assembly of RanBP2/RanGAP1-SUMO1/Ubc9 NPC subcomplex via phosphorylation of RanGAP1 by PKC-θ

The nuclear pore complex (NPC) is the sole and selective gateway for nuclear transport and its dysfunction has been associated with many diseases. The NPC subcomplex RanBP2, which consists of RanBP2 (Nup358), RanGAP1-SUMO1 and Ubc9, regulates the assembly and function of the NPC. The roles of immune signaling in NPC assembly remain poorly understood. Here, we show that, following TCR stimulation, protein kinase C-{theta} (PKC-{theta}) directly phosphorylates RanGAP1 to facilitate RanBP2 subcomplex assembly and nuclear import and, thus, the nuclear translocation of AP-1 transcription factor. Mechanistically, TCR stimulation induces the translocation of activated PKC-{theta} to the NPC, where it interacts with and phosphorylates RanGAP1 on Ser504 and Ser506. RanGAP1 phosphorylation increases its binding affinity for Ubc9, thereby promoting sumoylation of RanGAP1 and, finally, assembly of the RanBP2 subcomplex. Our findings reveal an unexpected role of PKC-{theta} as a direct regulator of nuclear import and uncover a phosphorylation-dependent sumoylation of RanGAP1, delineating a novel link between TCR signaling and assembly of the RanBP2 NPC subcomplex.

cell biology↗

bioRxiv2021

SNHG16 promotes cell proliferation and inhibits cell apoptosis via regulation of the miR-1303p/STARD9 axis in renal cell carcinoma

BackgroundRenal cell carcinoma (RCC) is a fatal malignant tumor with high morbidity. Numerous medical studies have suggested that long noncoding RNAs (lncRNAs) exert their biological function on various cancerous progresses. Herein, functions of lncRNA SNHG16 in RCC cells and the mechanism medicated by SNHG16 were investigated. MethodsThe expression levels of SNHG16 and its downstream genes in RCC cells and tissues were examined utilizing reverse transcription quantitative polymerase chain reaction analyses. Cell counting kit-8 and 5-Ethynyl-2-deoxyuridine assays were carried out to evaluate the proliferation of RCC cells, and flow cytometry analyses were employed to determine the apoptosis of RCC cells. Western blot analysis was applied to examine protein levels associated with cell proliferation and apoptosis. The combination between SNHG16 and miRNA as well as miRNA and its target gene were explored by luciferase reporter, RNA pull down, and RNA immunoprecipitation assays. ResultsThe significant upregulation of SNHG16 was observed in RCC tissues and cells. SNHG16 downregulation inhibited the proliferation and promoted the apoptosis of RCC cells. In addition, SNHG16 served as a competing endogenous RNA for miR-1301-3p, and STARD9 was a target gene of miR-1301-3p in RCC cells. SNHG16 upregulated STARD9 expression by binding with miR-1301-3p in RCC cells. Rescue assays validated that SNHG16 promoted RCC cell promotion and induced RCC cell apoptosis by upregulating STARD9 expression. ConclusionsSNHG16 promotes RCC cell proliferation and suppresses RCC cell apoptosis via interaction with miR-1301-3p to upregulate STARD9 expression in RCC cells.

cell biology↗