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  • 1
    In: Molecular Oncology, Wiley, Vol. 14, No. 10 ( 2020-10), p. 2589-2608
    Abstract: Cancer cells undergo epithelial‐to‐mesenchymal transition (EMT) in response to hypoxia. Exosomes produced in tumor microenvironments carry microRNAs (miRNAs) that affect proliferation, metastasis, and EMT. Hypoxic regulation of EMT is associated with telomerase content and stability, but the underlying mechanisms remain unclear. We identified a targeting relationship between tumor‐suppressing miR‐1255b‐5p and human telomerase reverse transcriptase (hTERT) via clinical screening of serum samples in colorectal cancer (CRC) patients. EMT suppression via exosomal miR‐1255b‐5p delivery was investigated by assessing hTERT expression, Wnt/β‐catenin signaling, and telomerase activity. We revealed that hypoxia directly affected exosomal miR‐1255b‐5p content, the delivery of which between CRC cells significantly impacted cell invasion, EMT‐related protein expression, and telomerase stability. Specifically, miR‐1255b‐5p suppressed EMT by inhibiting Wnt/β‐catenin activation via hTERT inhibition. Hypoxia reduced exosomal miR‐1255b‐5p secretion by CRC cells, thereby increasing hTERT expression to enhance EMT and telomerase activity. In a mouse CRC model, hypoxic exosomes containing overexpressed miR‐1255b‐5p attenuated EMT, tumor progression, and liver metastasis. Our results suggest the antitumor role of miR‐1255b‐5p and its involvement in the regulation of hTERT‐mediated EMT. We propose that miRNA‐targeted regulation of telomerase is a promising therapeutic strategy for future CRC treatment.
    Type of Medium: Online Resource
    ISSN: 1574-7891 , 1878-0261
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2322586-5
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  • 2
    In: The Clinical Respiratory Journal, Wiley, Vol. 17, No. 6 ( 2023-06), p. 536-547
    Abstract: The aetiological composition and clinical characteristics of patients with pulmonary hypertension (PH) hospitalised in the respiratory department were retrospectively analysed, as well as the correlation between transthoracic echocardiography (TTE) and right heart catheterization (RHC) for evaluating pulmonary artery systolic pressure (PASP) and mean pulmonary artery pressure (mPAP). Results Of 731 patients, 544 (74.42%) were diagnosed with PH by RHC. Pulmonary arterial hypertension (PAH) was the most common type of PH, accounting for 30.10%; PH due to lung disease and/or hypoxia accounted for 20.79%, and PH due to pulmonary artery obstructions accounted for 19.29%. TTE has the highest specificity for diagnosing PH due to pulmonary artery obstructions. The specificity was 0.9375, the sensitivity was 0.7361 and the area under the ROC curve (AUC) was 0.836. PASP, and mPAP estimated by TTE were different for various types of PH. In terms of PASP, TTE overestimated PASP in PH due to lung disease and/or hypoxia, but there was no significant difference compared with RHC (P  〉  0.05). TTE underestimates PAH patients' PASP compared with RHC. In terms of mPAP, TTE underestimated the mPAP of all types of PH, as there was a significant difference in the TTE‐estimated mPAP of patients with PAH compared with RHC but not on other types of PH. Pearson correlation analysis of TTE and RHC showed a moderate overall correlation (rPASP 0.598, P  〈  0.001; rmPAP 0.588, P  〈  0.001). Conclusions Among the patients with PH in the respiratory department, patients with PAH accounted for the majority. TTE has high sensitivity and specificity for the diagnosis of PH due to pulmonary artery obstructions in the respiratory department.
    Type of Medium: Online Resource
    ISSN: 1752-6981 , 1752-699X
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2442214-9
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