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1.
J Cell Mol Med ; 25(1): 61-72, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33332708

RESUMO

Long non-coding RNAs (lncRNAs) have been highlighted as attractive markers for diagnosis and prognosis as well as new therapeutic targets in multiple cancers, including nasopharyngeal carcinoma (NPC). Here, we attempted to investigate the underlying regulatory role of the lncRNA maternally expressed gene 3 (MEG3) in NPC development. As determined by RT-qPCR, MEG3 expression was down-regulated in NPC cells. Online RNA crosstalk analysis predicted the binding of miR-21 to MEG3 and PTEN, respectively. MEG3 was validated to bind to miR-21 while PTEN was identified as a target of miR-21 by dual-luciferase reporter gene assay. Exogenous transfection was done to change the levels of MEG3, miR-21 and PTEN in HK-1 cells to investigate their effects on the autophagy and apoptosis of NPC cells. The results suggested that MEG3 overexpression in HK-1 cells up-regulated PTEN and down-regulated miR-21, by which MEG3 further inhibited autophagy and apoptosis ability of NPC cells. The tumour formation ability was tested after injecting the HK-1 cells into nude, mice and tumour growth was monitored. Consistently, MEG3 overexpression inhibited the tumour formation in vivo. Collectively, MEG3 promotes the autophagy and apoptosis of NPC cells via enhancing PTEN expression by binding to miR-21.


Assuntos
Apoptose/genética , Autofagia/genética , MicroRNAs/metabolismo , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/patologia , PTEN Fosfo-Hidrolase/genética , RNA Longo não Codificante/metabolismo , Regulação para Cima/genética , Animais , Sequência de Bases , Carcinogênese/genética , Carcinogênese/patologia , Linhagem Celular Tumoral , Regulação para Baixo/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Modelos Biológicos , PTEN Fosfo-Hidrolase/metabolismo , Prognóstico , Ligação Proteica , RNA Longo não Codificante/genética
2.
Br J Radiol ; 94(1118): 20200870, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33332979

RESUMO

OBJECTIVES: To investigate the impact of deep learning (DL) on radiologists' detection accuracy and reading efficiency of rib fractures on CT. METHODS: Blunt chest trauma patients (n = 198) undergoing thin-slice CT were enrolled. Images were read by two radiologists (R1, R2) in three sessions: S1, unassisted reading; S2, assisted by DL as the concurrent reader; S3, DL as the second reader. The fractures detected by the readers and total reading time were documented. The reference standard for rib fractures was established by an expert panel. The sensitivity and false-positives per scan were calculated and compared among S1, S2, and S3. RESULTS: The reference standard identified 865 fractures on 713 ribs (102 patients) The sensitivity of S1, S2, and S3 was 82.8, 88.9, and 88.7% for R1, and 83.9, 88.7, and 88.8% for R2, respectively. The sensitivity of S2 and S3 was significantly higher compared to S1 for both readers (all p < 0.05). The sensitivity between S2 and S3 did not differ significantly (both p > 0.9). The false-positive per scan had no difference between sessions for R1 (p = 0.24) but was lower for S2 and S3 than S1 for R2 (both p < 0.05). Reading time decreased by 36% (R1) and 34% (R2) in S2 compared to S1. CONCLUSIONS: Using DL as a concurrent reader can improve the detection accuracy and reading efficiency for rib fracture. ADVANCES IN KNOWLEDGE: DL can be integrated into the radiology workflow to improve the accuracy and reading efficiency of CT rib fracture detection.


Assuntos
Aprendizado Profundo , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Fraturas das Costelas/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Estudos Retrospectivos , Costelas/diagnóstico por imagem , Costelas/lesões , Sensibilidade e Especificidade , Adulto Jovem
3.
Cancer Gene Ther ; 28(1-2): 74-88, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32555352

RESUMO

Cancer stem cells (CSCs) are responsible for tumor initiation, relapse, and metastasis. Thus, residual CSCs after chemotherapy may result in poor prognosis for nasopharyngeal carcinoma (NPC). Emerging evidence suggests that differentially expressed microRNAs (miRNAs) regulate genes that carry out important functions in CSCs. Here we investigate the interaction of microRNA-873 (miR-873) with the Zic family member 2 (ZIC2) and the effects on downstream serine-threonine protein kinase (AKT) signaling pathway in CSCs in the context of NPC. Initially, microarray-based gene expression profiling identified ZIC2 as a key differentially expressed gene in NPC, which was subsequently confirmed to be upregulated in clinical NPC tissue samples. NPC cells were subjected to sphere-formation conditions in low-attachment plates, followed by sorting of CD133+ cells, which were selected as NPC stem cells after further characterization of stem cell biomarkers. ZIC2 was then shown to be enriched in NPC stem cells at both mRNA and protein levels. However, loss of ZIC2 was associated with the self-renewal, proliferative and tumorigenic properties of NPC stem cells. Next, miRNAs potentially able to target ZIC2 were predicted by the intersection of mirDIP and TargetScan database results, and miRNA miR-873 was found to be downregulated in NPC tissues in general but especially in NPC stem cells. Upregulation of miR-873 inhibited the stem-like properties and tumorigenicity of NPC stem cells, which was found to take place through downregulation of ZIC2 and disruption of the AKT signaling pathway. Collectively, the results obtained suggest that overexpression of miR-873 could aid NPC tumor suppression through reduction of the malignant potential of CSCs.


Assuntos
MicroRNAs/metabolismo , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Proteínas Nucleares/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fatores de Transcrição/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Regulação para Baixo , Feminino , Genes Supressores de Tumor , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/patologia , Transdução de Sinais
4.
Chin Neurosurg J ; 5: 28, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-32922927

RESUMO

BACKGROUND: Spinal cord ischaemia animal models were established by selective ligation of the lumbar artery in a craniocaudal direction between the renal artery and the aortic bifurcation. Transcranial electrical stimulation motor-evoked potentials were measured to enable their use in future studies on spinal cord ischaemia protection. METHODS: Thirty-three New Zealand rabbits were randomly divided into 6 groups. Transcranial electrical stimulation motor-evoked potentials were recorded before vascular ligation, 30 min after vascular ligation, and 2 days after vascular ligation. Motor functions were assessed after surgery and 2 days after vascular ligation. The specimens were taken 2 days after ligation for histopathologic observation. RESULTS: With increased numbers of ligations, a transient extension of the latency became clear, but there were no significant differences in the statistical analysis. Analysis of variance after ligation at the same time in each group and t tests before and after ligation (P > 0.05) were not significant. One or 2 ligations did not cause spinal cord ischaemic damage. There were no significant differences before and after ligation for the amplitude (P > 0.05). With increased numbers of ligations, the amplitude before and after ligation was gradually reduced in the 3-5 ligation groups (P < 0.05). CONCLUSIONS: Ligation of segmental spinal cord vessels on 1 or 2 levels did not cause ischaemic damage. Spinal cord ischaemia was observed after 3, 4, or 5 ligations. The amplitude was more sensitive to spinal cord ischaemia than latency. Spinal cord function can be predicted by early changes in the amplitude.

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