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 language | English (US) |
|---|---|
| Article number | 63 |
| Journal | Molecular Cancer |
| Volume | 13 |
| Issue number | 1 |
| DOIs | |
| State | Published - Mar 20 2014 |
| Externally published | Yes |
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Keywords
- Combination therapy
- EGFR
- Glioblastoma
- miR-566
- Nimotuzumab
ASJC Scopus subject areas
- Cancer Research
- Molecular Medicine
- Oncology
Cite this
MicroRNA-566 activates EGFR signaling and its inhibition sensitizes glioblastoma cells to nimotuzumab. / Zhang, Kai Liang; Zhou, Xuan; Han, Lei; Chen, Lu Yue; Chen, Ling Chao; Shi, Zhen Dong; Yang, Ming; Ren, Yu; Yang, Jing Xuan; Frank, Thomas S.; Zhang, Chuan Bao; Zhang, Jun Xia; Pu, Pei Yu; Zhang, Jian Ning; Jiang, Tao; Wagner, Eric; Li, Min; Kang, Chun Sheng.
In: Molecular Cancer, Vol. 13, No. 1, 63, 20.03.2014.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - MicroRNA-566 activates EGFR signaling and its inhibition sensitizes glioblastoma cells to nimotuzumab
AU - Zhang, Kai Liang
AU - Zhou, Xuan
AU - Han, Lei
AU - Chen, Lu Yue
AU - Chen, Ling Chao
AU - Shi, Zhen Dong
AU - Yang, Ming
AU - Ren, Yu
AU - Yang, Jing Xuan
AU - Frank, Thomas S.
AU - Zhang, Chuan Bao
AU - Zhang, Jun Xia
AU - Pu, Pei Yu
AU - Zhang, Jian Ning
AU - Jiang, Tao
AU - Wagner, Eric
AU - Li, Min
AU - Kang, Chun Sheng
PY - 2014/3/20
Y1 - 2014/3/20
N2 - 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.
AB - 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.
KW - Combination therapy
KW - EGFR
KW - Glioblastoma
KW - miR-566
KW - Nimotuzumab
UR - http://www.scopus.com/inward/record.url?scp=84899582313&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84899582313&partnerID=8YFLogxK
U2 - 10.1186/1476-4598-13-63
DO - 10.1186/1476-4598-13-63
M3 - Article
C2 - 24650032
AN - SCOPUS:84899582313
VL - 13
JO - Molecular Cancer
JF - Molecular Cancer
SN - 1476-4598
IS - 1
M1 - 63
ER -