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1.
J Org Chem ; 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34236870

RESUMO

The Ir-catalyzed asymmetric hydrogenation of cyclic pyridinium salts is presented as a new strategy for the convenient and efficient synthesis of chiral indolizidines. The asymmetric hydrogenation of cyclic pyridinium salts derived from 2-(2-acylphenyl)pyridines proceeded smoothly in the presence of [Ir(cod)Cl]2 and (R)-DM-SegPhos to provide the desired chiral 7,8-benzoindolizidines 6 in high to excellent yields with moderate enantioselectivity (up to 86:14 er) and excellent diastereoselectivity (>20:1 dr). The enantiomeric purity of 6j was increased to 92:8 through recrystallization.

2.
J Mater Chem B ; 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34259306

RESUMO

A high-throughput and selective fluorimetric platform has been constructed for the analysis of ammonia in blood by using a polymer-stabilized metal-organic framework (MOF) of porous NH2-MIL-125, which was coated onto a wettable microwells array constructed on an indium tin oxide (ITO) substrate. It was found that the nitrogen plasma treatment for the ITO substrate could create a super-hydrophilic interface that combined with the hydrophobic pattern yielded a wettable microwells array, enabling the condensation-based enrichment of targets from the sample droplets. Moreover, the NH2-MIL-125 MOF encapsulated using polymers could be firmly coated onto the microwells to act as fluorescent probes for sensing NH3 with enhanced responses. In addition, the use of the polymer polyvinyl pyrrolidone could protect and stabilize the crystals of NH2-MIL-125 probe in aqueous media, revealing the improved hydrophilicity and significantly depressed signal background. The as-developed fluorimetric platform, containing a MOF-coated microwells array, can enable the detection of ammonia in blood, with concentrations ranging linearly from 0.10 to 300 µM. More importantly, this plasma treatment-based fabrication route may hold promise for designing different wettable microwells arrays for the high-throughput detection of multiple targets in the fields of biomedical analysis and environmental monitoring.

3.
J Mater Chem B ; 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34259308

RESUMO

A highly selective and sensitive photoelectrochemical (PEC) detection method has been developed for the analysis of copper (Cu2+) ions using nanoflower-like ZnO@CdS heterojunctions, of which ZnO was first in situ grown onto the indium tin oxide electrodes by a hydrothermal method and then coated with CdS through the chemical bath deposition route. It was discovered that the ZnO@CdS heterojunction so formed could serve as a photosensitive catalyst with improved charge separation for visible-light-driven PEC responses. Enhanced visible-light harvesting of nanocomposites could also be expected with CdS as the visible-light sensitizer. Furthermore, the introduction of Cu2+ ions could cause a rational decrease in the photocurrents of nanocomposites through the specific interaction between CdS and Cu2+ ions. A ZnO@CdS heterojunction-based PEC sensor was thereby developed for the detection of Cu2+ ions in blood in the linear concentrations ranging from 0.50 to 80 nM, with a limit of detection of 0.18 nM. Such a heterojunction-based PEC detection platform constructed using two photocatalytic materials with matched band structures are promising for a wide range of applications for sensing Cu2+ ions in clinical diagnostics, food monitoring, and environmental analysis.

4.
J Clin Invest ; 131(14)2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34263737

RESUMO

Anxiety-related disorders can be treated by cognitive therapies and transcranial magnetic stimulation, which involve the medial prefrontal cortex (mPFC). Subregions of the mPFC have been implicated in mediating different and even opposite roles in anxiety-related behaviors. However, precise causal targets of these top-down connections among diverse possibilities have not been established. Here, we show that the lateral septum (LS) and the central nucleus of the amygdala (CeA) represent 2 direct targets of the infralimbic cortex (IL), a subregion of the mPFC that modulates anxiety and fear. Two projections were unexpectedly found to exert opposite effects on the anxious state and learned freezing: the IL-LS projection promoted anxiety-related behaviors and fear-related freezing, whereas the IL-CeA projection exerted anxiolytic and fear-releasing effects for the same features. Furthermore, selective inhibition of corresponding circuit elements showed opposing behavioral effects compared with excitation. Notably, the IL-CeA projection implemented top-down control of the stress-induced high-anxiety state. These results suggest that distinct IL outputs exert opposite effects in modulating anxiety and fear and that modulating the excitability of these projections with distinct strategies may be beneficial for the treatment of anxiety disorders.

5.
J Agric Food Chem ; 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34260232

RESUMO

Drinking tea has been proven to have a positive biological effect in regulating human glucose and lipid metabolism and preventing type 2 diabetes (T2D). Skeletal muscle (SkM) is responsible for 70% of the sugar metabolism in the human body, and its dysfunction is an important factor leading to the development of obesity, T2D, and muscle diseases. As one of the four known theaflavins (TFs) in black tea, the biological role of theaflavin (TF1) in regulating SkM metabolism has not been reported. In this study, mature myotubes induced by C2C12 cells in vitro were used as models. The results showed that TF1 (20 µM) promoted mitochondrial abundance and glucose absorption in myotubes by activating the CaMKK2-AMPK signaling axis via Ca2+ influx. Moreover, it promoted the expression of slow muscle fiber marker genes (Myh7, Myl2, Tnnt1, and Tnnc1) and PGC-1α/SIRT1, as well as enhanced the oxidative phosphorylation capacity of myotubes. In conclusion, this study preliminarily clarified the potential role of TF1 in regulating SkM glucose absorption as well as promoting SkM mitochondrial biosynthesis and slow muscle fiber formation. It has potential research and application values for the prevention/alleviation of SkM-related T2D and Ca2+-related skeletal muscle diseases through diet.

6.
Artigo em Inglês | MEDLINE | ID: mdl-34288351

RESUMO

Phosphate-solubilizing microbes (PSMs) drive the biogeochemical cycling of phosphorus (P) and hold promise for sustainable agriculture. However, their global distribution, overall diversity and application potential remain unknown. Here, we present the first synthesis of their biogeography, diversity and utility, employing data from 399 papers published between 1981 and 2017, the results of a nationwide field survey in China consisting of 367 soil samples, and a genetic analysis of 12986 genome-sequenced prokaryotic strains. We show that at continental to global scales, the population density of PSMs in environmental samples is correlated with total P rather than pH. Remarkably, positive relationships exist between the population density of soil PSMs and available P, nitrate-nitrogen and dissolved organic carbon in soil, reflecting functional couplings between PSMs and microbes driving biogeochemical cycles of nitrogen and carbon. More than 2704 strains affiliated with at least nine archaeal, 88 fungal and 336 bacterial species were reported as PSMs. Only 2.59% of these strains have been tested for their efficiencies in improving crop growth or yield under field conditions, providing evidence that PSMs are more likely to exert positive effects on wheat growing in alkaline P-deficient soils. Our systematic genetic analysis reveals five promising PSM genera deserving much more attention.

7.
Curr Drug Metab ; 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34218778

RESUMO

BACKGROUND: Recently, the combination of Traditional Chinese Medicine (TCM) formulae and other drugs have been used frequently in clinical practice, while the possibility of herb-drug interaction (HDI) risk remains a challenge. Since metabolic enzymes mediate the majority of drug interactions, evaluating the effects of formulae on metabolic enzymes is instructive for the rational formulation of drug delivery plans. OBJECTIVE: Herein, we are devoted to estimating the effects of Zhenwu detection (ZWD) on activities and mRNA expression of 7 cytochrome P450 (CYP450) isoenzymes in chronic heart failure (CHF) rats. METHODS: The CHF rats were replicated by coronary artery ligation and were randomly divided into sham operation group, model group, ZWD low- (2.188 g/kg), middle- (4.375 g/kg), and high- (8.750 g/kg) dose groups, n=6. After 8 weeks, rats were administrated with ZWD and normal saline (NS) for four weeks. The mixed solution of 7 probe drugs (1 mL/kg) was subsequently injected into 30 rats through the caudal vein after the last administration. Pharmacokinetic parameters and mRNA expression of 7 probe drugs were measured by using UPLC-MS/MS and RT-qPCR, respectively. RESULTS: Activities and mRNA expression of CYP1A2, CYP2B1, CYP2C6, CYP2C11, CYP3A1 were inhibited in CHF rats, and ZWD could reverse this effect except for CYP2B1. CONCLUSION: Overall, these findings underscore that for CHF patients, the HDI should be taken into consideration when ZWD is used on its own or combined with drugs meditated by CYP1A2 (CYP1A2 in rats), CYP2C9 (CYP2C6 in rats), CYP2C19 (CYP2C11 in rats) and CYP3A4 (CYP3A1 in rats). Furthermore, since amodiaquine, dextromethorphan and bupropion apparent volume of distribution (Vd) were proved far greater than the total volume of body fluids, we speculate that the dose adjustment and potential organotoxicity of these substrates may need further consideration.

8.
Nanotechnology ; 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34225260

RESUMO

Group VA metal halide-based perovskites have emerged as intensively explored Pb-free perovskites, owing to their excellent environmental stability and low-toxicity. However, the relatively low carrier mobility and high photocarrier recombination rates restrict their applications in photodetectors. One promising approach to achieve higher performance is to integrate these Pb-free perovskites with 2D materials to form heterostructures. Here, we report on the high sensitivity photodetectors based on MoS2/Cs3Bi2I9 and graphene/Cs3Bi2I9 heterostructures for multispectral regions. The heterostructures combine the high carrier mobility of 2D materials with superior light-harvesting properties of perovskites, as well as the effective built-in electric filed at the junction area, leading to efficient photocarrier separation and extraction. The specific detectivity of MoS2/Cs3Bi2I9 device reaches 1.15×1013 Jones for the detection of UV light of 325 nm, which is four orders of magnitude higher than UV detectors built on GaN. As a result of the efficient dark current suppression, the specific detectivity of graphene/Cs3Bi2I9 photodetector can be promoted to 5.24×1011 Jones, 1.33×1011 Jones, and 1.12×1011 Jones for the detection of 325 nm, 447nm, and 532 nm light, respectively.

10.
Dev Cell ; 2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34214490

RESUMO

Lysosomes are the recycling center and nutrient signaling hub of the cell. Here, we show that lysosomes also control mesenchymal stem cell (MSC) differentiation by proteomic reprogramming. The chaperone-mediated autophagy (CMA) lysosome subgroup promotes osteogenesis, while suppressing adipogenesis, by selectively removing osteogenesis-deterring factors, especially master transcriptional factors, such as adipogenic TLE3, ZNF423, and chondrogenic SOX9. The activity of the CMA-committed lysosomes in MSCs are controlled by Van-Gogh-like 2 (Vangl2) at lysosomes. Vangl2 directly binds to lysosome-associated membrane protein 2A (LAMP-2A) and targets it for degradation. MSC-specific Vangl2 ablation in mice increases LAMP-2A expression and CMA-lysosome numbers, promoting bone formation while reducing marrow fat. The Vangl2:LAMP-2A ratio in MSCs correlates inversely with the capacity of the cells for osteoblastic differentiation in humans and mice. These findings demonstrate a critical role for lysosomes in MSC lineage acquisition and establish Vangl2-LAMP-2A signaling as a critical control mechanism.

11.
BMC Cancer ; 21(1): 697, 2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-34126961

RESUMO

BACKGROUND: Gastric cancer (GC) is one of the most common solid malignant tumors worldwide with a high-recurrence-rate. Identifying the molecular signatures and specific biomarkers of GC might provide novel clues for GC prognosis and targeted therapy. METHODS: Gene expression profiles were obtained from the ArrayExpress and Gene Expression Omnibus database. Differentially expressed genes (DEGs) were picked out by R software. The hub genes were screened by cytohubba plugin. Their prognostic values were assessed by Kaplan-Meier survival analyses and the gene expression profiling interactive analysis (GEPIA). Finally, qRT-PCR in GC tissue samples was established to validate these DEGs. RESULTS: Total of 295 DEGs were identified between GC and their corresponding normal adjacent tissue samples in E-MTAB-1440, GSE79973, GSE19826, GSE13911, GSE27342, GSE33335 and GSE56807 datasets, including 117 up-regulated and 178 down-regulated genes. Among them, 7 vital upregulated genes (HMMR, SPP1, FN1, CCNB1, CXCL8, MAD2L1 and CCNA2) were selected. Most of them had a significantly worse prognosis except SPP1. Using qRT-PCR, we validated that their transcriptions in our GC tumor tissue were upregulated except SPP1 and FN1, which correlated with tumor relapse and predicts poorer prognosis in GC patients. CONCLUSIONS: We have identified 5 upregulated DEGs (HMMR, CCNB1, CXCL8, MAD2L1, and CCNA2) in GC patients with poor prognosis using integrated bioinformatical methods, which could be potential biomarkers and therapeutic targets for GC treatment.

12.
Nat Commun ; 12(1): 3734, 2021 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-34145290

RESUMO

Genomic amplification of the distal portion of chromosome 3q, which encodes a number of oncogenic proteins, is one of the most frequent chromosomal abnormalities in malignancy. Here we functionally characterise a non-protein product of the 3q region, the long noncoding RNA (lncRNA) PLANE, which is upregulated in diverse cancer types through copy number gain as well as E2F1-mediated transcriptional activation. PLANE forms an RNA-RNA duplex with the nuclear receptor co-repressor 2 (NCOR2) pre-mRNA at intron 45, binds to heterogeneous ribonucleoprotein M (hnRNPM) and facilitates the association of hnRNPM with the intron, thus leading to repression of the alternative splicing (AS) event generating NCOR2-202, a major protein-coding NCOR2 AS variant. This is, at least in part, responsible for PLANE-mediated promotion of cancer cell proliferation and tumorigenicity. These results uncover the function and regulation of PLANE and suggest that PLANE may constitute a therapeutic target in the pan-cancer context.


Assuntos
Processamento Alternativo/genética , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias/genética , RNA Longo não Codificante/genética , Células A549 , Linhagem Celular Tumoral , Proliferação de Células/genética , Cromossomos Humanos Par 3/genética , Variações do Número de Cópias de DNA/genética , Fator de Transcrição E2F1/metabolismo , Células HCT116 , Ribonucleoproteínas Nucleares Heterogêneas Grupo M/genética , Humanos , Células MCF-7 , Neoplasias/patologia , Correpressor 2 de Receptor Nuclear/genética , Interferência de RNA , RNA Interferente Pequeno/genética
13.
Cancer Med ; 10(13): 4629-4643, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34121340

RESUMO

The tumor microenvironment (TME) is related to extracellular matrix (ECM) dynamics and has a broad fundamental and mechanistic role in tumorigenesis and cancer progression. We hypothesized that ECM regulators might play an essential role in pan-cancer attribution by causing a generic effect through its regulation of the dynamics of ECM alteration. By analyzing data from TCGA using GSEA and univariate Cox regression analysis, we found that ECM regulator genes were significantly enriched and contributed to mortality in various cancer types. Notably, UMAP analysis revealed that ECM regulator genes dominated the differences between tumor and adjacent normal tissues based on 59 or 31 pan-survival-related ECM gene sets. Subsequently, a five-gene signature consisting of the predominant ECM regulators ADAM12, MMP1, SERPINE1, PLOD3, and P4HA3 was identified. We found that this five-gene signature was pro-mortality in 18 types of cancer in TCGA, and validated eleven other cancer types in TCGA and seven types in the TARGET and CoMMpass databases using overall survival analysis. KEGG pathway enrichment and Pearson correlation analysis indicated that these five component genes that were correlated with specific ECM proteins involved in tumorigenesis from the ECM receptor interaction gene set. Additionally, the fitted results of a linear model were applied to strengthen the discovery, demonstrating that the five genes were correlated with immune infiltration score and especially associated with typically immunologically "cold" tumors. We thus conclude that the ADAM12, MMP1, SERPINE1, PLOD3, and P4HA3 signature showed a close association with a pan-cancer effect on prognosis and is related to ECM proteins in the TME which corresponding with immunologically "cold" cancer types.

14.
Int Immunopharmacol ; 98: 107869, 2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34153673

RESUMO

OBJECTIVE: Spondyloarthritis (SpA) is mainly characterized by bone erosion, new bone formation, inflammation and potential disability. Epigallocatechin gallate (EGCG) has been proved to be closely related with the regulation of inflammation and bone metabolism. However, whether EGCG could improve SpA remains unclear. METHODS: SpA animal model was established using proteoglycan. Cell proliferation were measured by CCK-8 assay. The mRNA expression levels of genes were detected using qRT-PCR, protein levels were assessed via western blotting and immunohistochemistry. ELISA assay was performed to examined the inflammatory cytokine release. Lesions in spine cartilage tissues were observed using hematoxylin-eosin (HE) and Safranin O staining. Alkaline phosphatase (ALP) assay and Alizarin Red S staining was used to investigate osteoblast mineralization. RESULTS: We found that EGCG could inhibit inflammation and new bone formation in SpA mice. Besides, inflammatory factor expression and osteogenic differentiation in osteoblasts isolated from SpA mice were also decreased by EGCG. Further, EGCG treatment suppressed the activation of Wnt/ß-Catenin/COX-2 pathway and the activator of this pathway partially reversed the effects of EGCG on inflammation and osteoblast differentiation. CONCLUSIONS: EGCG repressed inflammatory responses and new bone formation, and further improved SpA through Wnt/ß-Catenin/COX-2 pathway. Our findings may provide a new thought for the prevention and treatment of SpA.

15.
Nano Lett ; 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34061554

RESUMO

Oxide semiconductors are widely used in the photocatalytic fields, and introducing oxygen vacancies is an effective strategy to improve their photocatalytic efficiency. However, oxygen vacancies in the bulk often act as the recombination centers of electron-hole pairs, which accelerates the recombination of electron-hole pairs. In this paper, we propose a strategy of electric field treatment and apply it to a TiO2 film with oxygen vacancies to promote the photocatalytic efficiency. After treatment by an electric field, the conductive channels consisting of oxygen vacancies are formed in the TiO2 film, which greatly decreases the resistance by almost 6 × 103 times. The yield of CO can reach up to 1.729 mmol gcat-1 h-1, which is one of the best performances among the reported TiO2-based catalysts. This work provides an effective and feasible way for enhancing photocatalytic activity through an electric field, and this method is promising for wide use in the field of catalysis.

16.
Pharmazie ; 76(6): 244-248, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34078517

RESUMO

This study aimed to investigate the effect of metformin on osteoclast differentiation and apoptosis. Low concentration of metformin inhibited osteoclast differentiation and downregulated the expression of TRAP, RANK, Cathepsink, NFATC-1, MMP-9 and TRAF-6. High concentration of metformin promoted osteoclast apoptosis and upregulated the expression of Bax/Bcl-2 and caspase-3; BV/TV, BS/TV, Tb.N and BMD were increased while Tp.Sp decreased in the group of intraperitoneal metformin+femoral intramedullary osteoclast injection (Met+OC) compared with the control group, 1 nM metformin downregulated Akt, p44/42 MAPK, JNK, p38 MAPK phosphorylation, 5 nM metformin down regulated ERK and Akt phosphorylation. These results suggest that a low concentration of metformin inhibits osteoclast differentiation through PI3K/Akt and MAPK/ERK signaling pathway; high concentrations of metformin promote osteoclast apoptosis through PI3K/Akt and ERK signaling pathway.

17.
Physiol Genomics ; 2021 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-34121455

RESUMO

OBJECTIVE: Circular RNAs (circRNAs) function as promising biomarkers and therapeutic targets for coronary artery disease due to their high stability, covalently closed structure and potential gene regulation. We aimed to identify the expression profile and role of circular RNAs (circRNAs) in coronary artery disease (CAD). METHODS: We performed RNA sequence analysis of circRNAs in peripheral blood mononuclear cells of 5 CAD patients and 5 controls. Bioinformatics analyses was adopted to explore biological functions of differentially expressed circRNAs. The miRanda and TargetScan tools were used to predict the miRNA targeting interactions and to construct a triple network of differentially expressed gene-circRNA-miRNA-mRNA. RESULTS: In total, 13160 downregulated and 12905 upregulated circRNAs were identified in CAD. A gene ontology annotation analysis showed that genes in the network were involved in organelle organization, cell cycle, mitotic cycle and cellular metabolic process. Parental genes of the 10 dysregulated-circRNAs were involved in metabolism and protein modification, and these circRNAs might regulate gene expression associated with CAD via miRNA sponges. CONCLUSION: As potential ceRNAs, dysregulated circRNAs may be involved in the pathogenesis of CAD, which provides new insights into diagnosis and prognosis of coronary artery disease.

18.
Tree Physiol ; 2021 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-34137865

RESUMO

Male and female willow plants show spatial segregation of genders along the environmental gradients. Skewed gender ratio of willows is not only related to altitude, but also to nutrient status and sexual competition, which can affect their growth and defense by altering secondary metabolite production. The relationship between metabolites and nutrients in the two genders of Salix rehderiana was explored in the Gongga Mountain. We found gender ratio was altered with a change in soil nitrogen (N) status; in the high N habitats, secondary metabolites accumulated in males. Furthermore, pot experiment was conducted to test the effect of nitrogen supply on gender competition in S. rehderiana. Sufficient N supply stimulated females to produce amino acids and carbon-containing secondary metabolites for maintaining their carbon-nitrogen balance, but extra nitrogen for males was used for growth to occupy more space. N supply induced foliar nutrient imbalances and growth of opportunistic species, allowing them to outcompete neighbors. Better carbon allocation and storage in male than female willows would benefit intersexual competitiveness of males if environment N increases. Competition between the genders has a significant correlation with skewed gender ratio, spatial separation and resource utilization. Female willows would suffer fiercer competition for space by males with the increased soil N, which would result in the gender ratio alteration. Therefore, gender ratio of willows is likely to convert to gender balance from female-biased with long-term N deposition in the future.

19.
Photochem Photobiol ; 2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-34152605

RESUMO

We report relatively persistent, open-shell thiophene-based double helices, radical cations 1•+ -TMS12 and 2•+ -TMS8 . Closed-shell neutral double helices, 1-TMS12 and 2-TMS8 , have nearly identical first oxidation potentials, E+/0  ≈ +1.33 V, corresponding to reversible oxidation to their radical cations. The radical cations are generated, using tungsten hexachloride in dichloromethane (DCM) as an oxidant, E+/0  ≈ +1.56 V. EPR spectra consist of a relatively sharp singlet peak with an unusually low g-value of 2.001-2.002, thus suggesting exclusive delocalization of spin density over π-conjugated system consisting of carbon atoms only. DFT computations confirm these findings, as only negligible fraction of spin density is found on sulfur and silicon atoms and the spin density is delocalized over a single tetrathiophene moiety. For radical cation, 1•+ -TMS12 , energy level of the singly occupied molecular orbital (SOMO) lies below the four highest occupied molecular orbitals (HOMOs), thus indicating the SOMO-HOMO inversion (SHI) and therefore, violating the Aufbau principle. 1•+ -TMS12 has a half-life of the order of only 5 min at room temperature. EPR peak intensity of 2•+ -TMS8 , which does not show SHI, is practically unchanged over at least 2 h.

20.
Cell Death Dis ; 12(7): 627, 2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34145213

RESUMO

Long noncoding ribonucleic acids (LncRNAs) have been found to be involved in the proliferation, apoptosis, invasion, migration, and other pathological processes of triple-negative breast cancer (TNBC). Expression of the lncRNA actin filament-associated protein 1 antisense RNA1 (AFAP1-AS1) has been found to be significantly higher in TNBC than in other subtypes or in normal tissue samples, but the specific mechanism by which AFAP1-AS1 affects the occurrence and development of TNBC is yet to be revealed. In this study, we used Cell Counting Kit-8 (CCK-8), colony formation, wound healing migration, Transwell invasion, and nude mouse xenograft assays to confirm the role of AFAP1-AS1 in the proliferation, migration of TNBC cells in vitro and in vivo. In addition, we performed bioinformatics analyses, reverse transcriptase quantitative polymerase chain reaction (RT-qPCR), western blot (WB), and dual-luciferase reporter assays (dual-LRA) to confirm interaction among AFAP1-AS1, micro-RNA 2110 (miR-2110), and Sp1 transcription factor (Sp1). We found that silencing AFAP1-AS1 and Sp1 or upregulating miR-2110 suppressed the proliferation, migration, and invasion of MDA-MB-231 and MDA-MB-468 cells in vitro as well as tumor growth in vivo. Mechanistically, the dual-LRA highlighted that miR-2110 was an inhibitory target of AFAP1-AS1, and that AFAP1-AS1 functioned as a miR-2110 sponge to increase Sp1 expression. AFAP1-AS1 silencing led to a reduction in Sp1 mRNA and protein levels, which could be reversed by joint transfection with miR-2110 inhibitor. Our findings demonstrated that AFAP1-AS1 could modulate the progression of breast cancer cells and affect tumorigenesis in mice by acting as a miR-2110 sponge, resulting in regulation of Sp1 expression. Therefore, AFAP1-AS1 could play a pivotal role in the treatment of TNBC.

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