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Oncogenic miR-9 is a target of erlotinib in NSCLCs.
- Source :
-
Scientific reports [Sci Rep] 2015 Nov 23; Vol. 5, pp. 17031. Date of Electronic Publication: 2015 Nov 23. - Publication Year :
- 2015
-
Abstract
- EGFR-targeted cancer therapy is a breakthrough in non-small cell carcinoma. miRNAs have been proved to play important roles in cancer. Currently, for the role of miRNAs in EGFR-targeted cancer therapy is unclear. In this study, first we found that erlotinib reduced the expression of miR-9. MiR-9 expression was increased in human lung cancer tissues compared with peripheral normal tissues, and miR-9 promoted the growth of NSCLC cells. Overexpression of miR-9 decreased the growth inhibitory effect of erlotinib. Second, miR-9 decreased FoxO1 expression by directly inhibition of its mRNA translation. Adenovirus-mediated overexpression of FoxO1 or siRNA-mediated downregulation of FoxO1 negatively regulated cell growth. And exogenous overexpression FoxO1 reduced the pro-growth effect of miR-9. Finally, we found that erlotinib upregulated FoxO1 protein expression. Moreover, overexpression of miR-9 decreased erlotinib-induced FoxO1 expression, and overexpression of FoxO1 enhanced the growth inhibitory effects of erlotinib. Additionally, we found that erlotinib downregulates miR-9 expression through suppressing the transcrption of miR-9-1 and enhanced DNA methylation maybe involved. These findings suggest that oncogenic miR-9 targeted FoxO1 to promote cell growth, and downregulation of this axis was involved in erlotinib's growth inhibitory effects. Clarifying the regulation of miRNAs by erlotinib may indicate novel strategies for enhancing EGFR-targeted cancer therapy.
- Subjects :
- Base Sequence
Carcinoma, Non-Small-Cell Lung genetics
Carcinoma, Non-Small-Cell Lung metabolism
Carcinoma, Non-Small-Cell Lung pathology
Cell Line, Tumor
Cell Proliferation drug effects
DNA Methylation drug effects
Drug Resistance, Neoplasm
Forkhead Box Protein O1
Forkhead Transcription Factors antagonists & inhibitors
Forkhead Transcription Factors metabolism
Gene Expression Regulation, Neoplastic
Humans
Lung drug effects
Lung metabolism
Lung pathology
Lung Neoplasms genetics
Lung Neoplasms metabolism
Lung Neoplasms pathology
MicroRNAs metabolism
Molecular Sequence Data
Protein Biosynthesis
RNA, Messenger genetics
RNA, Messenger metabolism
RNA, Small Interfering genetics
RNA, Small Interfering metabolism
Signal Transduction
Antineoplastic Agents pharmacology
Carcinoma, Non-Small-Cell Lung drug therapy
Erlotinib Hydrochloride pharmacology
Forkhead Transcription Factors genetics
Lung Neoplasms drug therapy
MicroRNAs genetics
Protein Kinase Inhibitors pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 5
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 26593208
- Full Text :
- https://doi.org/10.1038/srep17031