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

研究成果: Article査読

20 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)1197-1210
ページ数14
ジャーナルJournal of Human Genetics
63
12
DOI
出版ステータスPublished - 01-12-2018
外部発表はい

All Science Journal Classification (ASJC) codes

  • 遺伝学
  • 遺伝学(臨床)

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