Long Noncoding RNA PVT1 Is Regulated by Bromodomain Protein BRD4 in Multiple Myeloma and Is Associated with Disease Progression

被引:19
作者
Handa, Hiroshi [1 ]
Honma, Kazuki [2 ]
Oda, Tsukasa [3 ]
Kobayashi, Nobuhiko [1 ]
Kuroda, Yuko [2 ]
Kimura-Masuda, Kei [2 ]
Watanabe, Saki [2 ]
Ishihara, Rei [2 ]
Murakami, Yuki [2 ]
Masuda, Yuta [2 ]
Tahara, Ken-ichi [1 ]
Takei, Hisashi [1 ]
Kasamatsu, Tetsuhiro [2 ]
Saitoh, Takayuki [2 ]
Murakami, Hirokazu [2 ]
机构
[1] Gunma Univ, Grad Sch Med, Dept Hematol, 3-39-22 Showa Machi, Maebashi, Gunma 3718511, Japan
[2] Gunma Univ, Grad Sch Hlth Sci, Dept Lab Sci, 3-39-22 Showa Machi, Maebashi, Gunma 3718511, Japan
[3] Gunma Univ, Inst Mol & Cellular Regulat, 3-39-22 Showa Machi, Maebashi, Gunma 3718511, Japan
关键词
long noncoding RNA; PVT1; MYC; bromodomain; multiple myeloma; LNCRNA PVT1; C-MYC; AMPLIFICATION; CANCER; LANDSCAPE;
D O I
10.3390/ijms21197121
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Long noncoding RNAs (lncRNAs) are deregulated in human cancers and are associated with disease progression. Plasmacytoma Variant Translocation 1 (PVT1), a lncRNA, is located adjacent to the gene MYC, which has been linked to multiple myeloma (MM). PVT1 is expressed in MM and is associated with carcinogenesis. However, its role and regulation remain uncertain. We examined PVT1/MYC expression using real-time PCR in plasma cells purified from 59 monoclonal gammopathy of undetermined significance (MGUS) and 140 MM patients. The MM cell lines KMS11, KMS12PE, OPM2, and RPMI8226 were treated with JQ1, an MYC super-enhancer inhibitor, or MYC inhibitor 10058-F4. The expression levels of PVT1 and MYC were significantly higher in MM than in MGUS (p < 0.0001) and were positively correlated with disease progression (r = 0.394, p < 0.0001). JQ1 inhibited cell proliferation and decreased the expression levels of MYC and PVT1. However, 10054-F4 did not alter the expression level of PVT1. The positive correlation between MYC and PVT1 in patients, the synchronous downregulation of MYC and PVT1 by JQ1, and the lack of effect of the MYC inhibitor on PVT1 expression suggest that the expression of these two genes is co-regulated by a super-enhancer. Cooperative effects between these two genes may contribute to MM pathogenesis and progression.
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页码:1 / 17
页数:17
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