Molecular pathogenesis of triple-negative breast cancer based on microRNA expression signatures: antitumor miR-204-5p targets AP1S3. Issue 12 (December 2018)

• Record Type: Journal Article
• Authors: Toda, Hiroko; Kurozumi, Sasagu; Kijima, Yuko; Idichi, Tetsuya; Shinden, Yoshiaki; Yamada, Yasutaka; Arai, Takayuki; Maemura, Kosei; Fujii, Takaaki; Horiguchi, Jun; Natsugoe, Shoji; Seki, Naohiko
• Is Part Of: Journal of human genetics. Volume 63:Issue 12(2018)
• Page Start: 1197
• Page End: 1210
• Publication Date: 2018-12
• Subjects: Medical genetics -- Periodicals; Human genetics -- Periodicals; 616.042
• DOI: 10.1038/s10038-018-0510-3
• Languages: English
• ISSNs: 1434-5161

Abstract

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 ofmiR-204-5p in breast cancer (BC) cells. Notably, cancer cell migration and invasion were significantly reduced by ectopic expression ofmiR-204-5p in BC cells. Genome-wide gene expression analysis and in silico database search revealed that 32 genes were putativemiR-204-5p targets. High expression ofAP1S3, RACGAP1, ELOVL6, andLRRC59 was significantly associated with poor prognosis in patients with BC, and adaptor-related protein complex 1 sigma 3 subunit (AP1S3 ) was directly regulated bymiR-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 byAP1S3 in BC cells. Overall, this miRNA signature is expected to be an effective tool for identification of miRNA-mediated molecular mechanisms of TNBC pathogenesis.