miR-367 stimulates Wnt cascade activation through degrading FBXW7 in NSCLC stem cells

Guodong Xiao, Boxiang Zhang, Jinying Meng, Jichang Wang, Chongwen Xu, Shou-Ching Tang, Xiang Li, Jing Zhang, Rui Liang, Hong Ren, Xin Sun

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Lung carcinoma tops the categories of cancer related motility, and has been treated as the main threat to human health. The functions and related mechanism of FBXW7 controlled lung cancer stem cells' signatures is barely unknown, and the miR-367 regulations of FBXW7 via Wnt signaling have not been explored. Cancer stem cells of either ALDH1+ or CD133+ phenotype were found to be referred to advanced stages in patients with NSCLC (non-small cell lung carcinoma). To study the roles of miR-367, we found greater miR-367 level or FBXW7 level was reserved in NSCLC than that of paired adjacent normal tissues, and their upregulations were positively correlated with Wnt signaling activation. On the contrary, increased miR-367 was correlated with Let-7 repression. MiR-367 was related to stronger sphere forming ability in stem cells of NSCLC. We then explored the functions of the endogenous miR-367 in stem-like cells isolated from NSCLC cell lines. In HEK-293 cells, we identified FBXW7 as the direct downstream gene of miR-367, which consequently released the LIN-28 dependent inhibition of suppressive Let-7. Through informatics analysis, miR-367 was predicated to function through Wnt signaling, and decreased Let-7 played the pivotal role to maintain TCF-4/Wnt pathway activity. The reintroduction of FBXW7 abolished the oncogenic stimulation of miR-367 on TCF-4 activity, with Wnt signaling factors depression. In conclusion, our findings demonstrated the oncogenic roles of miR-367 exerting on the self-renewal ability of cancer stem-like cells through degrading the suppressive FBXW7, eventually helping to maintain Wnt signaling activation through a LIN28B/Let-7 dependent manner.

Original languageEnglish (US)
Pages (from-to)2374-2385
Number of pages12
JournalCell Cycle
Volume16
Issue number24
DOIs
StatePublished - Dec 17 2017

Keywords

  • Cancer stem cells
  • FBXW7
  • Let-7
  • MiR-367
  • Wnt signaling

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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    Xiao, G., Zhang, B., Meng, J., Wang, J., Xu, C., Tang, S-C., Li, X., Zhang, J., Liang, R., Ren, H., & Sun, X. (2017). miR-367 stimulates Wnt cascade activation through degrading FBXW7 in NSCLC stem cells. Cell Cycle, 16(24), 2374-2385. https://doi.org/10.1080/15384101.2017.1380136