Molecular pathogenesis of triple-negative breast cancer based on microRNA expression signatures: antitumor miR-204-5p targets AP1S3

Hiroko Toda, Sasagu Kurozumi, Yuko Kijima, Tetsuya Idichi, Yoshiaki Shinden, Yasutaka Yamada, Takayuki Arai, Kosei Maemura, Takaaki Fujii, Jun Horiguchi, Shoji Natsugoe, Naohiko Seki

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1197-1210
Number of pages14
JournalJournal of Human Genetics
Volume63
Issue number12
DOIs
Publication statusPublished - 01-12-2018

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Fingerprint Dive into the research topics of 'Molecular pathogenesis of triple-negative breast cancer based on microRNA expression signatures: antitumor miR-204-5p targets AP1S3'. Together they form a unique fingerprint.

  • Cite this

    Toda, H., Kurozumi, S., Kijima, Y., Idichi, T., Shinden, Y., Yamada, Y., Arai, T., Maemura, K., Fujii, T., Horiguchi, J., Natsugoe, S., & Seki, N. (2018). Molecular pathogenesis of triple-negative breast cancer based on microRNA expression signatures: antitumor miR-204-5p targets AP1S3. Journal of Human Genetics, 63(12), 1197-1210. https://doi.org/10.1038/s10038-018-0510-3