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QKI, a miR-200 target gene, suppresses epithelial-to-mesenchymal transition and tumor growth

Title
QKI, a miR-200 target gene, suppresses epithelial-to-mesenchymal transition and tumor growth
Authors
Kim E.J.Kim J.S.Lee S.Lee H.Yoon J.-S.Hong J.H.Chun S.H.Sun D.S.Won H.S.Hong S.A.Kang K.Jo J.Y.Choi M.Shin D.H.Ahn Y.-H.Ko Y.H.
Ewha Authors
안영호
SCOPUS Author ID
안영호scopus
Issue Date
2019
Journal Title
International Journal of Cancer
ISSN
0020-7136JCR Link
Citation
International Journal of Cancer vol. 145, no. 6, pp. 1585 - 1595
Keywords
epithelial-to-mesenchymal transitionlung cancermiRNA-200oral cancerQKI
Publisher
Wiley-Liss Inc.
Indexed
SCIE; SCOPUS WOS scopus
Document Type
Article
Abstract
The microRNA-200 (miR-200) family plays a major role in specifying epithelial phenotype by preventing expression of the transcription repressors ZEB1 and ZEB2, which are well-known regulators of the epithelial-to-mesenchymal transition (EMT) in epithelial tumors including oral squamous cell carcinoma (OSCC). Here, we elucidated whether miR-200 family members control RNA-binding protein quaking (QKI), a newly identified tumor suppressor that is regulated during EMT. We predicted that miR-200a and miR-200b could recognize QKI 3′-UTR by analyzing TargetScan and The Cancer Genome Atlas head and neck squamous cell carcinoma (HNSCC) dataset. Forced expression of miR-200b/a/429 inhibited expression of ZEB1/2 and decreased cell migration in OSCC cell lines CAL27 and HSC3. QKI expression was also suppressed by miR-200 overexpression, and the 3′-UTR of QKI mRNA was directly targeted by miR-200 in luciferase reporter assays. Interestingly, shRNA-mediated knockdown of QKI led to pronounced EMT and protumor effects in both in vitro and in vivo studies of OSCC. Furthermore, high expression of QKI protein is associated with favorable prognosis in surgically resected HNSCC and lung adenocarcinoma. In conclusion, QKI increases during EMT and is targeted by miR-200; while, it suppresses EMT and tumorigenesis. We suggest that QKI and miR-200 form a negative feedback loop to maintain homeostatic responses to EMT-inducing signals. © 2019 UICC
DOI
10.1002/ijc.32372
Appears in Collections:
의과대학 > 의학과 > Journal papers
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