Overexpression of the long non-coding RNA PVT1 is correlated with leukemic cell proliferation in acute promyelocytic leukemia.
Overexpression of the long non-coding RNA PVT1 is correlated with leukemic cell proliferation in acute promyelocytic leukemia.
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长链非编码 RNA PVT1 的过度表达与急性早幼粒细胞白血病的白血病细胞增殖相关
DOI：
10.1186/s13045-015-0223-4
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发表时间：
2015-11-06
影响因子：
28.5
通讯作者：
Li Y
中科院分区：
文献类型：
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作者：
Zeng C;Yu X;Lai J;Yang L;Chen S;Li Y
背景急性早幼粒细胞白血病（APL）与染色体易位t(15;17)相关，导致形态异常的早幼粒细胞增殖。 8q24 染色体区域（包含 MYC 和 PVT1）的额外拷贝的获得已被证明是人类 APL 中最常见的继发性改变。 MYC升高可加速APL中粒细胞白血病的发展。然而，长链非编码RNA（lncRNA）PVT1的表达在APL发病机制中所起的作用仍不清楚。研究结果在本研究中，我们首先分析了28例新发APL患者外周血细胞中的lncRNA PVT1表达水平，发现与健康供者相比，APL患者中PVT1显着上调。然后，我们观察到 APL 细胞系中全反式维甲酸 (ATRA) 诱导的分化和细胞周期停滞期间 MYC 和 PVT1 表达显着降低。 NB4 细胞中 MYC 敲低导致 PVT1 下调。此外，通过RNA干扰敲低PVT1导致MYC蛋白水平受到抑制，细胞增殖受到抑制。结论我们的研究结果表明，lncRNA PVT1可能在APL细胞的增殖中发挥重要作用，并可能对未来的治疗管理有用。
BackgroundAcute promyelocytic leukemia (APL) is associated with chromosomal translocation t(15;17), which results in the proliferation of morphologically abnormal promyelocytes. Gain of supernumerary copies of the 8q24 chromosomal region, which harbors MYC and PVT1, has been shown to be the most common secondary alteration in human APL. Increased MYC can accelerate the development of myeloid leukemia in APL. However, the role that the expression of the long non-coding RNA (lncRNA) PVT1 plays in the pathogenesis of APL remains largely unknown.FindingsIn this study, we first analyzed the lncRNA PVT1 expression level in peripheral blood cells from 28 patients with de novo APL, and significantly upregulated PVT1 was found in APL patients compared with healthy donors. We then observed significantly lower MYC and PVT1 expression during all-transretinoic acid (ATRA)-induced differentiation and cell cycle arrest in the APL cell line. MYC knockdown in NB4 cells led to PVT1 downregulation. Moreover, PVT1 knockdown by RNA interference led to suppression of the MYC protein level, and cell proliferation was inhibited.ConclusionOur findings reveal that the lncRNA PVT1 may play an important role in the proliferation of APL cells and may be useful for future therapeutic management.