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

Eun Ju Kim, Jeong Seon Kim, Sieun Lee, Heejin Lee, Jung Sook Yoon, Ji Hyung Hong, Sang Hoon Chun, Der Sheng Sun, Hye Sung Won, Soon Auck Hong, Keunsoo Kang, Jeong Yeon Jo, Minyoung Choi, Dong Hoon Shin, Young Ho Ahn, Yoon Ho Ko

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

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.

Original languageEnglish
Pages (from-to)1585-1595
Number of pages11
JournalInternational Journal of Cancer
Volume145
Issue number6
DOIs
StatePublished - 15 Sep 2019

Keywords

  • QKI
  • epithelial-to-mesenchymal transition
  • lung cancer
  • miRNA-200
  • oral cancer

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