論文

査読有り 国際誌
2018年6月

Reduced expression of the H19 long non-coding RNA inhibits pancreatic cancer metastasis.

Laboratory investigation; a journal of technical methods and pathology
  • Hisashi Yoshimura
  • ,
  • Yoko Matsuda
  • ,
  • Masami Yamamoto
  • ,
  • Masaki Michishita
  • ,
  • Kimimasa Takahashi
  • ,
  • Norihiko Sasaki
  • ,
  • Naoshi Ishikawa
  • ,
  • Junko Aida
  • ,
  • Kaiyo Takubo
  • ,
  • Tomio Arai
  • ,
  • Toshiyuki Ishiwata

98
6
開始ページ
814
終了ページ
824
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/s41374-018-0048-1

H19 is an oncofetal RNA expressed in the developing embryo as well as in bladder, breast, gastric, pancreatic, hepatocellular, and prostate cancers. Recent studies have shown that H19 enhances cancer invasion and metastasis; however, its roles in cancer remain controversial. In the current study, H19 exhibited the second largest increase (82.4-fold) and represented the only non-protein coding gene among 11 genes identified that were elevated over 10-fold in lung-metastasis-derived pancreatic cancer cells compared with their parental cells using a mouse metastatic model. Subsequently, we further clarified the roles of H19 in pancreatic cancer growth and metastasis using in vitro and in vivo techniques. In situ hybridization showed that H19 was detected in 23 of 139 invasive ductal carcinomas (17%), and that H19 expression positively correlated with higher histological grades (P < 0.0001). Overexpression of H19 in PANC-1 pancreatic cancer cells induced higher motilities, whereas H19 inhibition using shRNA and siRNA showed opposite results; however, cell growth rates were not impacted. Intravenous injection of H19 shRNA vector-transfected PANC-1 cells yielded marked inhibition of metastasis in the liver and lungs of immunodeficient mice. These findings suggest that H19 has important roles in pancreatic cancer metastasis, and that inhibition of H19 represents a novel candidate for pancreatic cancer therapy.

リンク情報
DOI
https://doi.org/10.1038/s41374-018-0048-1
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/29581580