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1.
Nat Microbiol ; 9(5): 1256-1270, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38649412

RESUMO

Epstein-Barr virus (EBV) can infect both B cells and epithelial cells (ECs), causing diseases such as mononucleosis and cancer. It enters ECs via Ephrin receptor A2 (EphA2). The function of interferon-induced transmembrane protein-1 (IFITM1) in EBV infection of ECs remains elusive. Here we report that IFITM1 inhibits EphA2-mediated EBV entry into ECs. RNA-sequencing and clinical sample analysis show reduced IFITM1 in EBV-positive ECs and a negative correlation between IFITM1 level and EBV copy number. IFITM1 depletion increases EBV infection and vice versa. Exogenous soluble IFITM1 effectively prevents EBV infection in vitro and in vivo. Furthermore, three-dimensional structure prediction and site-directed mutagenesis demonstrate that IFITM1 interacts with EphA2 via its two specific residues, competitively blocking EphA2 binding to EBV glycoproteins. Finally, YTHDF3, an m6A reader, suppresses IFITM1 via degradation-related DEAD-box protein 5 (DDX5). Thus, this study underscores IFITM1's crucial role in blocking EphA2-mediated EBV entry into ECs, indicating its potential in preventing EBV infection.


Assuntos
Antígenos de Diferenciação , Efrina-A2 , Células Epiteliais , Infecções por Vírus Epstein-Barr , Herpesvirus Humano 4 , Receptor EphA2 , Internalização do Vírus , Humanos , Herpesvirus Humano 4/fisiologia , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/metabolismo , Células Epiteliais/virologia , Células Epiteliais/metabolismo , Infecções por Vírus Epstein-Barr/virologia , Infecções por Vírus Epstein-Barr/metabolismo , Receptor EphA2/metabolismo , Efrina-A2/metabolismo , Efrina-A2/genética , Antígenos de Diferenciação/metabolismo , Antígenos de Diferenciação/genética , Animais , Células HEK293 , Ligação Proteica , Camundongos , Linhagem Celular
2.
Am J Transl Res ; 15(1): 82-98, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36777845

RESUMO

OBJECTIVES: Circular RNAs (circRNAs) are involved in carcinogenesis, though their expression profile in renal cell carcinoma (RCC) is uncharacterized. The tumor suppressor gene miR-145-5p is expressed in RCC tissues, but its relationship with circRNAs is unknown. Thus, we aimed to identify differentially expressed circRNAs in RCC tissues and to explore the interaction between these circRNAs and miR-145 in the development of RCC. METHODS: We performed high-throughput sequencing and bioinformatics analyses to examine the expression pattern of circRNAs in RCC. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were used to functionally annotate differentially expressed circRNAs. Quantitative real-time polymerase chain reaction (qRT-PCR) was used for sequence verification. Small interfering RNAs were employed to investigate the function and mechanism of circRNAs in RCC. The relationship between miR-145-5p and circRNAs was confirmed using luciferase, RNA immunoprecipitation (RIP), and biotin-coupled probe RNA pull-down assays. RESULTS: Fifty-three circRNAs were significantly and differentially expressed in RCC compared to normal control tissue. Bioinformatic analyses indicated that two significantly upregulated circRNAs, circ-AFF2 and circ-ASAP1, had sequences corresponding to miR-145 response elements. Consistently, the luciferase reporter, RIP, and biotin-coupled probe RNA pull-down assays showed that circ-AFF2 and circ-ASAP1 may repress miR-145 by acting as sponges. circ-AFF2 and circ-ASAP1 were highly expressed in RCC patient-derived tumor samples; their overexpression correlated with poor prognosis and low miR-145 levels. Knockdown of circ-AFF2 or circ-ASAP1 in RCC cell lines inhibited proliferation, underscoring their oncogenic function. A circRNA-miRNA network was constructed for RCC using the differentially expressed circRNAs and projected miRNAs. Candidate genes were verified by RT-qPCR and western blot, indicating that circ-AFF2 and circ-ASAP1 may be connected to RCC proliferation and metastasis. CONCLUSION: circ-AFF2 and circ-ASAP1 were upregulated in RCC and likely promote tumor progression by sponging miR-145. Therefore, both circRNAs should be investigated further as potential diagnostic and therapeutic targets for RCC.

3.
World J Clin Cases ; 10(5): 1517-1526, 2022 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-35211589

RESUMO

BACKGROUND: Patients with benign prostatic disease often experience detrusor morphological changes and dysfunction. In severe cases, it leads to bladder detrusor dysfunction, resulting in dysuria, frequent urination, urgent urination, incomplete urination, and other symptoms including renal function injury. An operation to restore normal urination function and to control postoperative complications, as far as possible, is the most common method for benign prostatic disease. AIM: To observe the effect of precise nursing service mode on postoperative urinary incontinence prevention in patients with prostate disease. METHODS: In total, 130 patients diagnosed with benign prostatic disease, from January 2018 to June 2021, in our hospital, were selected and divided into observation and control groups according to their treatment options. Sixty-five cases in the control group were given routine nursing mode intervention and 65 cases in the observation group received precise nursing service mode intervention. The intervention with the observation group included psychological counseling about negative emotions, pelvic floor exercises, and post-hospital discharge care. The complications of the two groups were counted, and the general postoperative conditions of the two groups were recorded. The urinary flow dynamics indexes of the two groups were detected, and differences in clinical international prostate system score (IPSS) and urinary incontinence quality of life questionnaire (I-QOL) scores were evaluated. RESULTS: Postoperative exhaust time (18.65 ± 3.23 h and 24.63 ± 4.51 h), the time of indwelling catheter (4.85 ± 1.08 d and 5.63 ± 1.24 d), and hospitalization time (8.78 ± 2.03 d and 10.23 ± 2.28 d) in the observation group were lower than in the control group. The difference was statistically significant (P < 0.05). After the operation, the maximum urinary flow rate (Qmax) increased (P < 0.05), the residual urine volume (RUV) decreased (P < 0.05), and the maximum closed urethral pressure (MUCP) was not statistically significant (P > 0.05) compared to pre-operation. The Qmax of the observation group was higher than that of the control group, while the RUV was lower than that of the control group. There was no significant difference in MUCP between the observation and control groups (P > 0.05). The I-QOL score of the two groups improved (P < 0.05), and the IPSS decreased (P < 0.05). After the operation, the I-QOL score of the observation group was higher than that of the control group, and the IPSS was lower than that of the control group (P < 0.05). There were no significant differences in the incidence of urethral injury (1.54% and 3.08%), bladder spasm (0.00% and 1.54%), and secondary bleeding (1.54% and 4.62) between the observation and control groups (P > 0.05). CONCLUSION: The precise nursing service mode can reduce the incidence of postoperative urinary incontinence in patients with prostate disease, thus improving postoperative urodynamics and rehabilitation, and quality of life.

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