論文

査読有り
2017年11月

Long non-coding RNA MALAT1 is an inducible stress response gene associated with extramedullary spread and poor prognosis of multiple myeloma

BRITISH JOURNAL OF HAEMATOLOGY
  • Hiroshi Handa
  • ,
  • Yuko Kuroda
  • ,
  • Kei Kimura
  • ,
  • Yuta Masuda
  • ,
  • Hikaru Hattori
  • ,
  • Lobna Alkebsi
  • ,
  • Morio Matsumoto
  • ,
  • Tetsuhiro Kasamatsu
  • ,
  • Nobuhiko Kobayashi
  • ,
  • Ken-ichi Tahara
  • ,
  • Makiko Takizawa
  • ,
  • Hiromi Koiso
  • ,
  • Takuma Ishizaki
  • ,
  • Hiroaki Shimizu
  • ,
  • Akihiko Yokohama
  • ,
  • Norifumi Tsukamoto
  • ,
  • Takayuki Saito
  • ,
  • Hirokazu Murakami

179
3
開始ページ
449
終了ページ
460
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1111/bjh.14882
出版者・発行元
WILEY

Extramedullary myeloma (EMM) occurs when myeloma develops outside the bone marrow; it often develops after chemotherapy and is associated with the acquisition of chemo-resistance and a fatal course. The mechanisms underlying extramedullary spread have not yet been fully elucidated. MALAT1 is a highly abundantly and ubiquitously expressed long non-coding RNA that plays important roles in cancer metastasis. The aims of this study were to clarify the association of MALAT1 with EMM and to elucidate the underlying mechanism of EMM formation under chemotherapeutic pressure. MALAT1 expression was significantly higher in multiple myeloma (MM) than in monoclonal gammopathy of undetermined significance. Furthermore, MALAT1 expression was markedly higher in EMM compared with that in corresponding intramedullary myeloma cells. A higher MALAT1 level was associated with shorter overall and progression-free survival. MALAT1 expression level was positively correlated with expression of HSP90AA1, HSP90AB1 and HSP90B1 but not with TP53 expression. MALAT1 was significantly upregulated by bortezomib and doxorubicin. Considering the known functions of MALAT1, our results suggest that it acts as a stress response gene that is upregulated by chemotherapy, thereby linking chemotherapy to EMM formation. Elucidating the biological implication of long non-coding RNA contributes to deeper understanding concerning the pathogenesis and investigation of novel therapeutic targets for MM.

Web of Science ® 被引用回数 : 27

リンク情報
DOI
https://doi.org/10.1111/bjh.14882
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/28770558
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000413676800012&DestApp=WOS_CPL