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Molecular pathogenesis of triple-negative breast cancer based on microRNA expression signatures: antitumor miR-204-5p targets AP1S3
- Source :
- Journal of Human Genetics. 63:1197-1210
- Publication Year :
- 2018
- Publisher :
- Springer Science and Business Media LLC, 2018.
-
Abstract
- Triple-negative breast cancer (TNBC) is an aggressive type of cancer associated with a poor prognosis. Identification of novel therapeutic targets in TNBC is urgently needed. Here, we investigated the microRNA (miRNA) expression signature of TNBC using clinical specimens. In total, 104 miRNAs (56 upregulated and 48 downregulated) were significantly dysregulated in TNBC tissues; miR-204-5p showed the most dramatic downregulation. We then examined the antitumor roles of miR-204-5p in breast cancer (BC) cells. Notably, cancer cell migration and invasion were significantly reduced by ectopic expression of miR-204-5p in BC cells. Genome-wide gene expression analysis and in silico database search revealed that 32 genes were putative miR-204-5p targets. High expression of AP1S3, RACGAP1, ELOVL6, and LRRC59 was significantly associated with poor prognosis in patients with BC, and adaptor-related protein complex 1 sigma 3 subunit (AP1S3) was directly regulated by miR-204-5p, as demonstrated by luciferase reporter assays. AP1S3 overexpression was detected in TNBC clinical specimens and enhanced cancer cell aggressiveness. We further analyzed downstream RNA networks regulated by AP1S3 in BC cells. Overall, this miRNA signature is expected to be an effective tool for identification of miRNA-mediated molecular mechanisms of TNBC pathogenesis.
- Subjects :
- 0301 basic medicine
Triple Negative Breast Neoplasms
Biology
03 medical and health sciences
0302 clinical medicine
Breast cancer
Downregulation and upregulation
Cell Movement
Cell Line, Tumor
microRNA
Gene expression
Genetics
medicine
Humans
Neoplasm Invasiveness
RNA, Neoplasm
Genetics (clinical)
Triple-negative breast cancer
Cancer
medicine.disease
Neoplasm Proteins
Gene Expression Regulation, Neoplastic
MicroRNAs
030104 developmental biology
030220 oncology & carcinogenesis
Cancer cell
Cancer research
Female
Ectopic expression
Genome-Wide Association Study
Subjects
Details
- ISSN :
- 1435232X and 14345161
- Volume :
- 63
- Database :
- OpenAIRE
- Journal :
- Journal of Human Genetics
- Accession number :
- edsair.doi.dedup.....1ba57e000568fb503120d6bc69a760db