MicroRNA-566 activates EGFR signaling and its inhibition sensitizes glioblastoma cells to nimotuzumab

Kai Liang Zhang, Xuan Zhou, Lei Han, Lu Yue Chen, Ling Chao Chen, Zhen Dong Shi, Ming Yang, Yu Ren, Jing Xuan Yang, Thomas S. Frank, Chuan Bao Zhang, Jun Xia Zhang, Pei Yu Pu, Jian Ning Zhang, Tao Jiang, Eric Wagner, Min Li, Chun Sheng Kang

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Background: Epidermal growth factor receptor (EGFR) is amplified in 40% of human glioblastomas. However, most glioblastoma patients respond poorly to anti-EGFR therapy. MicroRNAs can function as either oncogenes or tumor suppressor genes, and have been shown to play an important role in cancer cell proliferation, invasion and apoptosis. Whether microRNAs can impact the therapeutic effects of EGFR inhibitors in glioblastoma is unknown.Methods: miR-566 expression levels were detected in glioma cell lines, using real-time quantitative RT-PCR (qRT-PCR). Luciferase reporter assays and Western blots were used to validate VHL as a direct target gene of miR-566. Cell proliferation, invasion, cell cycle distribution and apoptosis were also examined to confirm whether miR-566 inhibition could sensitize anti-EGFR therapy.Results: In this study, we demonstrated that miR-566 is up-regulated in human glioma cell lines and inhibition of miR-566 decreased the activity of the EGFR pathway. Lentiviral mediated inhibition of miR-566 in glioblastoma cell lines significantly inhibited cell proliferation and invasion and led to cell cycle arrest in the G0/G1 phase. In addition, we identified von Hippel-Lindau (VHL) as a novel functional target of miR-566. VHL regulates the formation of the β-catenin/hypoxia-inducible factors-1α complex under miR-566 regulation.Conclusions: miR-566 activated EGFR signaling and its inhibition sensitized glioblastoma cells to anti-EGFR therapy.

Original languageEnglish (US)
Article number63
JournalMolecular Cancer
Volume13
Issue number1
DOIs
StatePublished - Mar 20 2014
Externally publishedYes

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Keywords

  • Combination therapy
  • EGFR
  • Glioblastoma
  • miR-566
  • Nimotuzumab

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Oncology

Cite this

Zhang, K. L., Zhou, X., Han, L., Chen, L. Y., Chen, L. C., Shi, Z. D., Yang, M., Ren, Y., Yang, J. X., Frank, T. S., Zhang, C. B., Zhang, J. X., Pu, P. Y., Zhang, J. N., Jiang, T., Wagner, E., Li, M., & Kang, C. S. (2014). MicroRNA-566 activates EGFR signaling and its inhibition sensitizes glioblastoma cells to nimotuzumab. Molecular Cancer, 13(1), [63]. https://doi.org/10.1186/1476-4598-13-63