3 years ago

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

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

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/bjh.14882

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