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1.
Heliyon ; 10(5): e26976, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38463788

RESUMO

Background: Glioma, a highly resistant and recurrent type of central nervous system tumor, poses a significant challenge in terms of effective drug treatments and its associated mortality rates. Despite the discovery of Ferredoxin 1 (FDX1) as a crucial participant in cuproptosis, an innovative mechanism of cellular demise, its precise implications for glioma prognosis and tumor immune infiltration remain inadequately elucidated. Methods: To analyze pan-cancer data, we employed multiple public databases. Gene expression evaluation was performed using tissue microarray (TMA) and single-cell sequencing data. Furthermore, four different approaches were employed to assess the prognostic importance of FDX1 in glioma. We conducted the analysis of differential expression genes (DEGs) and Gene Set Enrichment Analysis (GSEA) to identify immune-related predictive signaling pathways. Somatic mutations were assessed using Tumor Mutation Burden (TMB) and waterfall plots. Immune cell infiltration was evaluated with five different algorithms. Furthermore, we performed in vitro investigations to evaluate the biological roles of FDX1 in glioma. Results: Glioma samples exhibited upregulation of FDX1, which in turn predicted poor prognosis and was positively associated with unfavorable clinicopathological characteristics. Notably, the top four enriched signaling pathways were immune-related, and the discovery revealed a connection between the expression of FDX1 and the frequency of mutations or the TMB. The FDX1_high group exhibited heightened infiltration of immune cells, and there existed a direct association between the expression of FDX1 and the regulation of immune checkpoint. In vitro experiments demonstrated that FDX1 knockdown reduced proliferation, migration, invasion and transition from G2 to M phase in glioma cells. Conclusion: In glioma, FDX1 demonstrated a positive association with the advancement of malignancy and changes in the infiltration of immune cells.

2.
Mol Neurobiol ; 2024 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-38519735

RESUMO

Spinal cord injury (SCI) is a serious disease without effective therapeutic strategies. To identify the potential treatments for SCI, it is extremely important to explore the underlying mechanism. Current studies demonstrate that anoikis might play an important role in SCI. In this study, we aimed to identify the key anoikis-related genes (ARGs) providing therapeutic targets for SCI. The mRNA expression matrix of GSE45006 was downloaded from the Gene Expression Omnibus (GEO) database, and the ARGs were downloaded from the Molecular Signatures Database (MSigDB database). Then, the potential differentially expressed ARGs were identified. Next, correlation analysis, gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and protein-protein interaction (PPI) analysis were employed for the differentially expressed ARGs. Moreover, miRNA-gene networks were constructed by the hub ARGs. Finally, RNA expression of the top ten hub ARGs was validated in the SCI cell model and rat SCI model. A total of 27 common differentially expressed ARGs were identified at different time points (1, 3, 7, and 14 days) following SCI. The GO and KEGG enrichment analysis of these ARGs indicated several enriched terms related to proliferation, cell cycle, and apoptotic process. The PPI results revealed that most of the ARGs interacted with each other. Ten hub ARGs were further screened, and all the 10 genes were validated in the SCI cell model. In the rat model, only seven genes were validated eventually. We identified 27 differentially expressed ARGs of the SCI through bioinformatic analysis. Seven real hub ARGs (CCND1, FN1, IGF1, MYC, STAT3, TGFB1, and TP53) were identified eventually. These results may expand our understanding of SCI and contribute to the exploration of potential SCI targets.

3.
Int J Surg ; 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38348893

RESUMO

IMPORTANCE: Patients with pCR of rectal cancer following neoadjuvant treatment had better oncological outcomes. However, reliable methods for accurately predicting pCR remain limited. OBJECTIVE: To evaluate whether transrectal ultrasound-guided tru-cut biopsy (TRUS-TCB) adds diagnostic value to conventional modalities for predicting pathological complete response (pCR) in patients with rectal cancer after neoadjuvant treatment. DESIGN, SETTING, AND PARTICIPANTS: This study evaluated data of patients with rectal cancer who were treated with neoadjuvant treatment and reassessed using TRUS-TCB and conventional modalities before surgery. This study is registered with ClinicalTrials.gov. MAIN OUTCOMES AND MEASURES: The primary outcome was accuracy, along with secondary outcomes including sensitivity, specificity, negative predictive value, and positive predictive value in predicting tumor residues. Final surgical pathology was used as reference standard. RESULTS: Between June 2021 and June 2022, a total of 74 patients were enrolled, with 63 patients ultimately evaluated. Among them, 17 patients (28%) exhibited a complete pathological response. TRUS-TCB demonstrated an accuracy of 0.71 (95% CI, 0.58-0.82) in predicting tumor residues. The combined use of TRUS-TCB and conventional modalities significantly improved diagnostic accuracy compared to conventional modalities alone (0.75 vs. 0.59, P=0.02). Furthermore, TRUS-TCB correctly reclassified 52% of patients erroneously classified as having a complete clinical response by conventional methods. The occurrence of only one mild adverse event was observed. CONCLUSIONS AND RELEVANCE: Transrectal ultrasound-guided tru-cut biopsy (TRUS-TCB) proves to be a safe and accessible tool for reevaluation with minimal complications. The incorporation of TRUS-TCB alongside conventional methods leads to enhanced diagnostic performance.

4.
Bioact Mater ; 35: 242-258, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38333615

RESUMO

Induced pluripotent stem cells (iPSCs) can be personalized and differentiated into neural stem cells (NSCs), thereby effectively providing a source of transplanted cells for spinal cord injury (SCI). To further improve the repair efficiency of SCI, we designed a functional neural network tissue based on TrkC-modified iPSC-derived NSCs and a CBD-NT3-modified linear-ordered collagen scaffold (LOCS). We confirmed that transplantation of this tissue regenerated neurons and synapses, improved the microenvironment of the injured area, enhanced remodeling of the extracellular matrix, and promoted functional recovery of the hind limbs in a rat SCI model with complete transection. RNA sequencing and metabolomic analyses also confirmed the repair effect of this tissue from multiple perspectives and revealed its potential mechanism for treating SCI. Together, we constructed a functional neural network tissue using human iPSCs-derived NSCs as seed cells based on the interaction of receptors and ligands for the first time. This tissue can effectively improve the therapeutic effect of SCI, thus confirming the feasibility of human iPSCs-derived NSCs and LOCS for SCI repair and providing a valuable direction for SCI research.

5.
Front Immunol ; 14: 1291385, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38022537

RESUMO

Backgrounds: Disulfidptosis, a newly discovered mechanism of programmed cell death, is believed to have a unique role in elucidating cancer progression and guiding cancer therapy strategies. However, no studies have yet explored this mechanism in glioma. Methods: We downloaded data on glioma patients from online databases to address this gap. Subsequently, we identified disulfidptosis-related genes from published literature and verified the associated lncRNAs. Results: Through univariate, multivariate, and least absolute shrinkage and selection operator (LASSO) regression algorithms analyses, we identified 10 lncRNAs. These were then utilized to construct prognostic prediction models, culminating in a risk-scoring signature. Reliability and validity tests demonstrated that the model effectively discerns glioma patients' prognosis outcomes. We also analyzed the relationship between the risk score and immune characteristics, and identified several drugs that may be effective for high-risk patients. In vitro experiments revealed that LINC02525 could enhances glioma cells' migration and invasion capacities. Additionally, knocking down LINC02525 was observed to promote glioma cell disulfidptosis. Conclusion: This study delves into disulfidptosis-related lncRNAs in glioma, offering novel insights into glioma therapeutic strategies.


Assuntos
Glioma , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , Reprodutibilidade dos Testes , Prognóstico , Glioma/genética , Algoritmos
6.
PLoS One ; 18(11): e0293986, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37922307

RESUMO

BACKGROUND: Acute respiratory failure (ARF) is a common disease in the intensive care units (ICUs) with high risk of mortality. The red cell distribution width (RDW) is one of baseline ICU indicators which can be easily available, and has been used in the long-term prognostic analyses of diseases. However, no studies have explored the role of baseline RDW and its change during hospitalization in in-hospital mortality in ARF. Herein, this study aims to explore the association between RDW and its changes and the 30-day mortality in ARF patients. METHODS: Demographic and clinical data of 7,497 patients with ARF were extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database in 2012-2019 in this retrospective cohort study. Univariable and multivariable Cox regression analyses were used to explore the association between RDW and its changes and 30-day mortality with hazard ratios (HRs) and 95% confidence intervals (CIs). Subgroup analyses of different baseline RDW levels were also performed. We then assessed the predictive performance of RDW changes combined with the Sequential Organ Failure Assessment (SOFA) score on 30-day mortality using receiver operator characteristic curves (ROCs) with areas under curve (AUCs). RESULTS: Totally, 2,254 (30.07%) patients died in 30 days. After adjusting for covariates, we found that high baseline RDW [HR = 1.25, 95%CI: (1.15-1.37)] and RDW changes ≥0.3% [HR = 1.12, 95%CI: (1.01-1.24)] were both related to an increased risk of 30-day mortality. In patients whose baseline RDW level ≥14.9%, RDW changes ≥0.3% was also associated with an increased risk of 30-day mortality [HR = 1.19, 95%CI: (1.05-1.35)]. Moreover, the predictive value of RDW changes combined with SOFA on 30-day mortality was a little better than that of single SOFA score, with AUCs of 0.624 vs. 0.620. CONCLUSION: High baseline RDW level and its changes during hospitalization was relate to the increased risk of 30-day mortality in ARF, and the predictive value of RDW changes for ARF short-term mortality is still needed exploration.


Assuntos
Índices de Eritrócitos , Insuficiência Respiratória , Humanos , Estudos Retrospectivos , Cuidados Críticos , Unidades de Terapia Intensiva , Prognóstico
8.
Chem Commun (Camb) ; 59(77): 11576-11579, 2023 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-37691517

RESUMO

A comprehensive study was conducted to investigate the failure mechanism of the lithium metal anode (LMA) in air. Simultaneously, an effective reactivation strategy was developed using halogen regulation. Specifically, iodine treatment converts the passivation layer of the exposed Li into LiI with fast Li+ transport ability, thereby improving the electrochemical performance.

9.
Nano Lett ; 23(18): 8481-8489, 2023 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-37669545

RESUMO

Pursuing high-energy-density lithium metal batteries (LMBs) necessitates the advancement of electrolytes. Despite demonstrating high compatibility with lithium metal anodes (LMAs), ether-based electrolytes face challenges in achieving stable cycling at high voltages. Herein, we propose a strategy to enhance the high-voltage stability of medium-concentration (∼1 M) ether electrolytes by altering the reaction pathway of ether solvents. By employing a 1 M lithium difluoro(oxalato)borate in dimethoxyethane (LiDFOB/DME) electrolyte, we observed that LiDFOB displays a pronounced tendency for decomposition over DME, leading to a modification in the decomposition pathway of DME. This modification facilitates the formation of a stable organic-inorganic hybrid interface. Utilizing such an electrolyte, the Li-LCO cell demonstrates a discharge specific capacity of 146 mAh g-1 (5 C) and maintains retention of 86% over 1000 cycles at 2 C under a 4.5 V cutoff voltage. Additionally, the optimized ether electrolyte demonstrated outstanding cycling performance in Li-LCO full cells under practical conditions.

10.
Bioeng Transl Med ; 8(1): e10368, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36684111

RESUMO

Near-infrared (NIR) photothermal therapy plays a critical role in the cancer treatment and diagnosis as a promising carcinoma treatment modalities nowadays. However, development of clinical application has been greatly limited due to the inefficient drug release and low tumor accumulation. Herein, we designed a NIR-light triggered indocyanine green (ICG)-based PCL core/P(MEO2MA-b-HMAM) shell nanocomposites (PPH@ICG) and evaluated their therapeutic effects in vitro and in vivo. The anticancer drug 5-fluorouracil (5Fu) and the photothermal agent ICG were loaded into a thermo-sensitive micelle (PPH@5Fu@ICG) by self-assembly. The nanoparticles formed were characterized using transmission electron microscopy, dynamic light scattering, and fluorescence spectra. The thermo-sensitive copolymer (PPH@5Fu@ICG) showed a great temperature-controlled drug release response with lower critical solution temperature. In vitro cellular uptake and TEM imaging proved that PPH@5Fu@ICG nanoparticles can home into the lysosomal compartments under NIR. Moreover, in gastric tumor-bearing nude mice, PPH@5Fu@ICG + NIR group exhibited excellent improvement in antitumor efficacy based on the NIR-triggered thermo-chemotherapy synergy, both in vitro and in vivo. In summary, the proposed strategy of synergistic photo-hyperthermia chemotherapy effectively reduced the 5Fu dose, toxic or side effect, which could serve as a secure and efficient approach for cancer theranostics.

11.
Front Oncol ; 12: 1013419, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36408161

RESUMO

Background: Rosai-Dorfman disease (RDD) is a rare benign non-Langerhans cell histiocytic proliferative disease. RDD with central nervous system (CNS) involvement (CNS-RDD) is extremely rare. Its etiology is unclear, and there are no consensus recommendations for its treatment. More studies are needed to elucidate the clinical and radiological manifestations and prognosis of CNS-RDD. Methods: From January 2012 to June 2022, 12 patients with CNS-RDD (intracranial or spinal) were retrospectively evaluated, including collecting clinical data, imaging data, and pathological findings; summarizing imaging characteristics; and conducting follow-up studies on CND-RDD patient treatment and prognosis. Results: Twelve CNS-RDD patients (nine male and three female patients, aged 12-67 years) were enrolled in this study. Nine patients represented convex and/or skull base RDD (eight with edema, six with lobulation and/or pseudopodium sign, four with multiple intracranial lesions), two patients had parenchymal RDD, and one patient had spinal cord subdural lesions. Symptoms of patients would vary according to the locations of the lesion, including but not limited to headaches, dizziness, seizures, cranial nerve dysfunction, and visual impairment. The immunohistochemistry of RDD showed positive expression of S100 and CD68 but not CD1a. Total resection (n = 7), subtotal resection (n = 3), partial resection (n = 1), and stereotaxic biopsy (n = 1) were achieved, respectively. A combination of chemotherapy plus steroid therapy was performed on two patients (relapsing case and residual lesion) and showed a remarkable effect. Conclusion: CNS-RDD, as a rare disease, presents a significant diagnostic challenge for clinicians. Solitary CNS-RDD are easily misdiagnosed as meningioma. However, when the MRI imaging of the disease represents dura-based masses with significant edema, homogeneous enhancement, lobulation, and/or pseudopodium sign, we should consider it might be the CNS-RDD. Surgery is an important and effective therapy for CNS-RDD. Steroids and chemotherapy are safe and effective for the postoperative treatment of relapsing cases or residual lesions.

12.
Chem Commun (Camb) ; 58(89): 12463-12466, 2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36264058

RESUMO

A low-concentration (0.5 M) all-fluorinated electrolyte (LCAFE) was designed to stabilize high-energy-density lithium metal batteries. Introducing fluorinated solvents can control the electrolyte's solvation structure, interfacial chemistry, and physicochemical properties. Therefore, this LCAFE has good wettability, nonflammability, and excellent stability for lithium anodes.

13.
Front Surg ; 9: 919276, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35937594

RESUMO

Background: Frontal sinus exposure is a common consequence of frontal craniotomy. Cerebrospinal fluid leakage and infection are the major postoperative complications that may occur as a result of the open frontal sinus. The successful filling of the open frontal sinus provides an approach to prevent significant complications caused by frontal sinus exposure. Objective: This article describes a new technique to reconstruct the exposed frontal sinus cavity with the combined application of gelatin sponge and a vascularized pericranial flap. Methods: A total of 140 patients underwent frontal sinus reconstruction using gelfoam and vascularized pericranial flaps from 2016 to 2021. Gelatin sponge was used to fill the frontal sinus, and a vascularized pericranial flap was used to cover the frontal sinus when the bone flap was retracted. Results: Postoperative cerebrospinal fluid leakage and infection did not occur in any patient. Conclusion: Our results validated the effectiveness of our technique in the prevention of exposed frontal sinus-related postoperative complications.

14.
Bioengineered ; 13(1): 810-823, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34974791

RESUMO

The dysregulated circular RNAs (circRNAs) are linked to progression and chemoresistance in colorectal cancer (CRC). However, the role of circRNA protein tyrosine kinase 2 (circPTK2) in CRC progression and chemoresistance is uncertain. The circPTK2, microRNA (miR)-136-5p, m6A 'reader' protein YTH domain family protein 1 (YTHDF1), ß-catenin and cyclin D1 abundances were examined via quantitative reverse transcription PCR or Western blotting. The progression was investigated by cell counting kit-8 (CCK-8), colony formation, transwell and xenograft analysis. The resistance to 5-fluorouracil (5-FU) and oxaliplatin was analyzed via detecting cell viability and apoptosis using CCK-8 analysis and flow cytometry. The binding relationship was examined through dual-luciferase reporter, RNA immunoprecipitation and pull-down analysis. In our study, circPTK2 abundance was enhanced in CRC and associated with liver metastasis, clinical stage and chemoresistance. CircPTK2 knockdown constrained cell proliferation, migration, invasion, resistance to 5-FU and oxaliplatin, and the Wnt/ß-catenin signaling. MiR-136-5p was bound with circPTK2 and downregulated in CRC. MiR-136-5p knockdown attenuated the influence of circPTK2 silence on CRC progression and chemoresistance. YTHDF1 was targeted via miR-136-5p and upregulated in CRC samples and cells. MiR-136-5p targeted YTHDF1 to restrain CRC progression and chemoresistance. In addition, we confirmed that circPTK2 silence reduced xenograft tumor growth. In conclusion, circPTK2 interference suppressed CRC proliferation, migration, invasion and chemoresistance via regulating miR-136-5p and YTHDF1.Abbreviations: circRNAs: circular RNAs; CRC: colorectal cancer; circPTK2: circRNA protein tyrosine kinase 2; miR: microRNA; YTHDF1: YTH domain family protein 1; CCK-8: cell counting kit-8; 5-FU: 5-fluorouracil; RIP: RNA immunoprecipitation.


Assuntos
Antineoplásicos/farmacologia , Neoplasias Colorretais/patologia , Resistencia a Medicamentos Antineoplásicos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , MicroRNAs/genética , RNA Circular/genética , Proteínas de Ligação a RNA/genética , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Neoplasias Colorretais/genética , Progressão da Doença , Regulação para Baixo , Fluoruracila/farmacologia , Regulação Neoplásica da Expressão Gênica , Células HT29 , Humanos , Neoplasias Hepáticas/genética , Masculino , Camundongos , Estadiamento de Neoplasias , Transplante de Neoplasias , Oxaliplatina/farmacologia , Via de Sinalização Wnt
15.
iScience ; 25(1): 103490, 2022 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-35005528

RESUMO

Developing low cost, yet high-voltage electrolyte is significant to improve the energy density and practicability of lithium metal batteries (LMBs). Low concentration electrolyte has significant merits in terms of cost and viscosity; however, their poor compatibility with high-voltage LMBs hinders its applications. Here, we develop a diluted low concentration electrolyte by replacing solvating cosolvent with a non-solvating cosolvent to facilitate the interaction between BF4 - and Li+, resulting in optimized interfacial chemistry and suppressed side reaction. Thus, the high-loading Li-LiCoO2 full cells (20.4 mg cm-2) deliver outstanding cycling stability and rate performance at a cutoff voltage of 4.6 V. More impressively, a Li-LiCoO2 pouch cell achieves an energy density of more than 400 Wh kg-1 under practical conditions with thin Li (50 µm) and lean electrolyte (2.7 g Ah-1). This work provides a rational approach to design a low concentration electrolyte, which can be extended to other high voltage battery systems.

16.
Front Neurorobot ; 16: 1104559, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36687206

RESUMO

In this research, an image defogging algorithm is proposed for the electricity transmission line monitoring system in the smart city. The electricity transmission line image is typically situated in the top part of the image which is rather thin in size. Because the electricity transmission line is situated outside, there is frequently a sizable amount of sky in the backdrop. Firstly, an optimized quadtree segmentation method for calculating global atmospheric light is proposed, which gives higher weight to the upper part of the image with the sky region. This prevents interference from bright objects on the ground and guarantees that the global atmospheric light is computed in the top section of the image with the sky region. Secondly, a method of transmission calculation based on dark pixels is introduced. Finally, a detail sharpening post-processing based on visibility level and air light level is introduced to enhance the detail level of electricity transmission lines in the defogging image. Experimental results indicate that the algorithm performs well in enhancing the image details, preventing image distortion and avoiding image oversaturation.

17.
Risk Manag Healthc Policy ; 14: 5005-5014, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34938136

RESUMO

BACKGROUND: The quarantine in dedicated hotels has become an inevitable safety measure due to the frequent cross-border travel since the outbreak of COVID-19. The aim of the present study was to explore the trends in the psychological status of individuals entering from high-risk areas of COVID-19 coronavirus while quarantining in dedicated hotels. METHODS: A total of 591 individuals who isolated in dedicated hotels were recruited between March and June 2020. Participants self-reported mental symptoms [Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS)] every three days during the quarantine. A mixed-effects linear regression model was used to assess the trends. RESULTS: Participants reporting anxiety and depression symptoms at least one time during quarantine accounted for 4.5% and 18.4%, respectively. Their psychological status was alleviated during some first 9 days, and then it slightly deteriorated, which was suggested by SAS and SDS scores that were negatively correlated with the days of quarantine (T) (adjusted coefficient [ß] -0.81, 95% CI -1.00 to -0.62; and ß -0.75, 95% CI -0.97 to -0.53, respectively), and were positively correlated with the square of T (ß 0.04, 95% CI 0.02 to 0.06; and ß 0.04, 95% CI 0.02 to 0.06, respectively). The unemployed and 18~30-year-old participants were prone to greater levels of psychological distress. No significant difference in the trend of mental health was found among different subgroups. CONCLUSION: The mental health of the people entering Guangzhou from high-risk areas of COVID-19 coronavirus resulted positive during the early period of quarantine in dedicated hotels, after which it deteriorated. The psychological status of individuals should be closely monitored at the beginning and after more than 9 days of quarantine, especially for individuals who are unemployed and 18~30-year-old ones.

18.
Med Sci Monit ; 27: e935765, 2021 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-34903707

RESUMO

This publication has been retracted by the Editor due to the identification of non-original figure images and manuscript content that raise concerns regarding the credibility and originality of the study and the manuscript. Reference: Huashe Wang, Zhipeng Jiang, Honglei Chen, Xiaobin Wu, Jun Xiang, Junsheng Peng. MicroRNA-495 Inhibits Gastric Cancer Cell Migration and Invasion Possibly via Targeting High Mobility Group AT-Hook 2 (HMGA2). Med Sci Monit, 2017; 23: 640-648. DOI: 10.12659/MSM.898740.

19.
Bioengineered ; 12(2): 11277-11287, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34874224

RESUMO

A great many microRNAs (miRNAs) have been reported to play different roles in human cancers, including gastric cancer (GC). However, the specific character of miR-23a-3p in GC has not been elucidated. This study was to explore the function of miR-23a-3p in GC. The results manifested that miR-23a-3p was down-regulated in GC and patients with reduced miR-23a-3p had poor prognosis. Functional experiments assured that elevated miR-23a-3p refrained GC proliferation, invasion, migration, PIK3/Akt phosphorylation and apoptosis, while knockdown miR-23a-3p accelerated the growth of GC. Double luciferase report experiments manifested that miR-23a-3p targeted CCL22 expression. Functional rescue experiments affirmed that the repression of elevated miR-23a-3p on GC was reversed by simultaneous augmented CCL22. In vivo, elevated miR-23a-3p restrained the volume and tumor of GC and reduced the expression of CCL22 and phosphorylated PIK3/Akt, while knockdown miR-23a-3p motivated tumor growth. In conclusion, the results of this study indicate that miR-23a-3p plays a repressive role in GC, and affects the progression of GC via down-regulating CCL22 and blocking PI3K/AKT signal transduction pathway, which may offer a new molecular target for clinical treatment of GC.


Assuntos
Quimiocina CCL22/metabolismo , MicroRNAs/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Neoplasias Gástricas/genética , Animais , Sequência de Bases , Linhagem Celular Tumoral , Sobrevivência Celular/genética , Progressão da Doença , Regulação para Baixo/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Transdução de Sinais/genética
20.
Cancer Cell Int ; 21(1): 596, 2021 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-34742305

RESUMO

AIM: Previous studies have reported that circular RNA (circRNA) is associated with the pathogenesis of CRC. This study was designed to reveal the mechanism of circ-ring finger protein 121 (circ-RNF121) in colorectal cancer (CRC). MATERIALS AND METHODS: The levels of circ-RNF121, microRNA-1224-5p (miR-1224-5p) and forkhead box M1 (FOXM1) were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Protein level was detected by western blot. Cell proliferation was analyzed by 3-(4,5-Dimethylthazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and cell colony formation assays. Flow cytometry analysis was performed to investigate cell apoptosis. Cell migration and invasion were investigated by transwell and wound-healing assays. Cell glycolysis was detected using glucose, lactate and ADP/ATP ratio assay kits. The binding relationship between miR-1224-5p and circ-RNF121 or FOXM1 was predicted by starBase online database, and identified by dual-luciferase reporter assay. The impacts of circ-RNF121 silencing on tumor formation in vivo were disclosed by in vivo tumor formation assay. KEY FINDINGS: Circ-RNF121 and FOXM1 expression were dramatically upregulated, while miR-1224-5p expression was downregulated in CRC tissues or cells compared with control groups. Circ-RNF121 silencing repressed cell proliferation, migration, invasion and glycolysis but induced cell apoptosis in CRC, which were attenuated by miR-1224-5p inhibitor. Additionally, circ-RNF121 acted as a sponge of miR-1224-5p and miR-1224-5p bound to FOXM1. Circ-RNF121 silencing inhibited tumor growth in vivo. Furthermore, circ-RNF121 was secreted through being packaged into exosomes. SIGNIFICANCE: The finding provided a novel insight into studying circRNA-mediated CRC therapy.

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