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Background

Breast cancer is the most prevalent cancer among women, and AXL and MET are the key genes in the PI3K/AKT/mTOR pathway as critical elements in proliferation and invasion of cancer cells. MicroRNAs (miRNAs) are small non-coding RNAs regulating the expression of genes.

Methods

Bioinformatic approaches were used to find a miRNA that simultaneously targets both AXL and MET 3'-UTRs. The expression of target miRNA was evaluated in triple-negative (MDA-MB-231) and HER2-overexpressing (SK-BR-3) breast cancer cell lines as well as normal breast cells, MCF-10A, using quantitative real-time PCR. Then, the miRNA was overexpressed in normal and cancer cell lines using a lentiviral vector system. Afterwards, effects of overexpressed miRNA on the expression of AXL and MET genes were evaluated using quantitative real-time PCR.

Results

By applying bioinformatic software and programs, miRNAs that target the 3'-UTR of both AXL and MET mRNAs were determined, and according to the scores, miR-34a was selected for further analyses. The expression level of miR-34a in MDA-MB-231 and SK-BR-3 was lower than that of MCF-10A. Furthermore, AXL and MET expression in SK-BR-3 and MDA-MB-231 was lower and higher, respectively, than that of MCF-10A. After miR-34a overexpression, MET and AXL were downregulated in MDA-MB-231. In addition, MET was downregulated in SK-BR-3, while AXL was upregulated in this cell line.

Conclusions

These findings may indicate that miR-34a is an oncogenic miRNA, downregulated in the distinct breast cancer subtypes. It also targets MET and AXL 3'-UTRs in triple-negative breast cancer. Therefore, it can be considered as a therapeutic target in this type of breast cancer."xsd:string
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http://purl.uniprot.org/citations/30386383http://purl.uniprot.org/core/author"Mohammadi-Yeganeh S."xsd:string
http://purl.uniprot.org/citations/30386383http://purl.uniprot.org/core/author"Paryan M."xsd:string
http://purl.uniprot.org/citations/30386383http://purl.uniprot.org/core/author"Hajalirezay Yazdi S."xsd:string
http://purl.uniprot.org/citations/30386383http://purl.uniprot.org/core/date"2018"xsd:gYear
http://purl.uniprot.org/citations/30386383http://purl.uniprot.org/core/name"Cell Mol Biol Lett"xsd:string
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http://purl.uniprot.org/citations/30386383http://purl.uniprot.org/core/title"An integrated approach of bioinformatic prediction and in vitro analysis identified that miR-34a targets MET and AXL in triple-negative breast cancer."xsd:string
http://purl.uniprot.org/citations/30386383http://purl.uniprot.org/core/volume"23"xsd:string
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