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Comprehensive gene and microRNA expression profiling reveals miR-206 inhibits MET in lung cancer metastasis
- Source :
- Molecular BioSystems. 11:2290-2302
- Publication Year :
- 2015
- Publisher :
- Royal Society of Chemistry (RSC), 2015.
-
Abstract
- MiRNAs associated with the metastasis of lung cancer remain largely unexplored. In this study, gene and miRNA expression profiling were performed to analyze the global expression of mRNAs and miRNAs in human high- and low-metastatic lung cancer cell strains. By developing an integrated bioinformatics analysis, six miRNAs (miR-424-3p, miR-450b-5p, miR-335-5p, miR-34a-5p, miR-302b-3p and miR-206) showed higher target gene degrees in the miRNA-gene network and might be potential metastasis-related miRNAs. Using the qRT-PCR method, the six miRNAs were further confirmed to show a significant expression difference between human lung cancer and normal tissue samples. Since miR-206 showed lower expression both in lung cancer tissues and cell lines, it was used as an example for further functional verification. The wound healing assay and transwell invasion assay showed that miR-206 mimics significantly inhibited the cell migration and invasion of the high-metastatic lung cancer 95D cell strain. One of its predicted targets in our miRNA-gene network, MET, was also obviously decreased at the protein level when miR-206 was overexpressed. Instead, miR-206 inhibitors increased MET protein expression, cell migration and invasion of the low-metastatic lung cancer 95C cell strain. Meanwhile, the luciferase assay showed that MET was a direct target of miR-206. Furthermore, MET gene silence showed a similar anti-migration and anti-invasion effect with miR-206 mimics in 95D cells and could partially attenuate the migration- and invasion-promoting effect of miR-206 inhibitors in 95C cells, suggesting that miR-206 targets MET in lung cancer metastasis. Finally, we also demonstrated that miR-206 can significantly inhibit lung cancer proliferation and metastasis in mouse models. In conclusion, our study provided a miRNA-gene regulatory network in lung cancer metastasis and further demonstrated the roles of miR-206 and MET in this process, which enhances the understanding of the regulatory mechanism in lung cancer metastasis.
- Subjects :
- Adult
Male
Lung Neoplasms
Biology
Bioinformatics
Metastasis
Mice
Gentamicin protection assay
Cell Movement
Cell Line, Tumor
microRNA
medicine
Animals
Humans
Gene Regulatory Networks
Neoplasm Invasiveness
RNA, Messenger
Neoplasm Metastasis
Lung cancer
Molecular Biology
Aged
Cell Proliferation
Regulation of gene expression
Cell migration
Middle Aged
Proto-Oncogene Proteins c-met
medicine.disease
Xenograft Model Antitumor Assays
Gene Expression Regulation, Neoplastic
Gene expression profiling
MicroRNAs
Cell culture
Cancer research
Female
Biotechnology
Subjects
Details
- ISSN :
- 17422051 and 1742206X
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Molecular BioSystems
- Accession number :
- edsair.doi.dedup.....71ac724907c95b0d2a9fa0bf0a0114c2