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  • MiR-498 in esophageal squamous cell carcinoma: clinicopathological impacts and functional interactions

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    Author(s)
    Islam, Farhadul
    Gopalan, Vinod
    Law, Simon
    Tang, Johnny Cheuk-On
    Chan, Kwok-Wah
    Lam, Alfred King-Yin
    Griffith University Author(s)
    Lam, Alfred K.
    Gopalan, Vinod
    Islam, Farhad
    Year published
    2017
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    Abstract
    MicroRNA-498 plays a crucial role in progression of many carcinomas. The signaling pathways by which miR-498 modulates carcinogenesis are still unknown. Also, miR-498–associated molecular pathogenesis has never been studied in esophageal squamous cell carcinoma (ESCC). Herein, we aimed to examine the expression and functional roles of miR-498 in ESCC as well as its influences on the clinicopathological features in patients with ESCC. Expression of miR-498 was investigated in 93 ESCC tissues and 5 ESCC cell lines using quantitative real-time polymerase chain reaction. In vitro effects of miR-498 on cellular process were studied ...
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    MicroRNA-498 plays a crucial role in progression of many carcinomas. The signaling pathways by which miR-498 modulates carcinogenesis are still unknown. Also, miR-498–associated molecular pathogenesis has never been studied in esophageal squamous cell carcinoma (ESCC). Herein, we aimed to examine the expression and functional roles of miR-498 in ESCC as well as its influences on the clinicopathological features in patients with ESCC. Expression of miR-498 was investigated in 93 ESCC tissues and 5 ESCC cell lines using quantitative real-time polymerase chain reaction. In vitro effects of miR-498 on cellular process were studied followed by overexpression of miR-498. Western blot and immunofluorescence techniques were used to identify the interacting targets for miR-498 in ESCC. miR-498 expression was significantly reduced in ESCC when compared with the nonneoplastic esophageal tissues (P < .05). Patients with low miR-498 expression showed different histological grading of cancer and survival rates when compared with the patients with high miR-498 expression. Overexpression of miR-498 in ESCC cell lines induced remarkable reductions of cell proliferation, barrier penetration, and colony formation when compared with control and wild-type counterparts. Also, miR-498 activated the FOXO1/KLF6 transcriptional axis in ESCC. In addition, miR-498 overexpression increased p21 protein expression and led to reduced cancer cell growth. To conclude, reduced expression of miR-498 in ESCC and in vitro analysis have confirmed the tumor suppressor properties of miR-498 by modulating the FOXO1/KLF6 signaling pathway. The changes in miR-498 expression may have impacts on the clinical pathological parameters of ESCC as well as in the management of the patients with ESCC.
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    Journal Title
    Human Pathology
    Volume
    62
    DOI
    https://doi.org/10.1016/j.humpath.2017.01.014
    Copyright Statement
    © 2017 Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (http://creativecommons.org/licenses/by-nc-nd/4.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, providing that the work is properly cited.
    Subject
    Clinical sciences
    Pathology (excl. oral pathology)
    Publication URI
    http://hdl.handle.net/10072/343055
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    • Journal articles

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