在白血病细胞中发现的长链非编码RNA（lncRNA）或许会影响酪氨酸激酶靶向白血病疗法的疗效，而目前lncRNA CCDC26的功能并没有被完全解析，而来自广岛大学的研究者则在杂志Molecular Cancer上刊登了他们的最新研究成果，研究者在文章中揭示了CCDC26控制受体酪氨酸激酶KIT表达的机制，相关研究结果或为理解白血病的复发且帮助开发白血病疗法提供一定的帮助。

　　近来转录组学的相关研究发现了相对较长但并未转录翻译成为蛋白的大量RNAs，其中lncRNA被认为可以调节其它基因的表达，而机体中lncRNAs的突变或失衡往往会引发一系列疾病，比如癌症，然而lncRNAs的分子功能目前尚未被阐明。

　　研究者Tetsuo Hirano表示，我们发现细胞中名为lncRNA CCDC26的基因的敲除会明显上调KIT基因的表达，而KIT基因的过度表达则在急性髓性白血病中被发现；研究者发现CCDC26的转录在人类髓样白血病细胞系的细胞核碎片中处于较高的水平，同时CCDC26的敲除会诱发CCDC26 包含内含子的转录物的抑制，进而导致转录基因被抑制。CCDC26敲除的白血病细胞往往在血清剥除后的生存期会延长，而KIT特殊的抑制剂则会逆转细胞生存期的延长。

　　最后研究者表示，CCDC26可以通过调节KIT基因的表达来控制髓样白血病细胞的生长，异常的CCDC26 RNA结构会调整KIT的表达从而诱导意想不到的基因表达；因此以CCDC26拷贝数突变为主要特性的白血病或许可以通过靶向作用KIT的疗法来进行治疗。

　　doi:10.1186/s12943-015-0364-7

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　　PMID:

　　Long noncoding RNA, CCDC26, controls myeloid leukemia cell growth through regulation of KIT expression

　　Tetsuo Hirano1*, Ryoko Yoshikawa1, Hironori Harada2, Yuka Harada2, Atsuhiko Ishida1 and Takeshi Yamazaki1

　　Background Accumulating evidence suggests that some long noncoding RNAs (lncRNAs) are involved in certain diseases, such as cancer. The lncRNA, CCDC26, is related to childhood acute myeloid leukemia (AML) because its copy number is altered in AML patients. Results We found that CCDC26 transcripts were abundant in the nuclear fraction of K562 human myeloid leukemia cells. To examine the function of CCDC26, gene knockdown (KD) was performed using short hairpin RNAs (shRNAs), and four KD clones, in which CCDC26 expression was suppressed to 1% of its normal level, were isolated. This down-regulation included suppression of CCDC26 intron-containing transcripts (the CCDC26 precursor mRNA), indicating that transcriptional gene suppression (TGS), not post-transcriptional suppression, was occurring. The shRNA targeting one of the two CCDC26 splice variants also suppressed the other splice variant, which is further evidence for TGS. Growth rates of KD clones were reduced compared with non-KD control cells in media containing normal or high serum concentrations. In contrast, enhanced growth rates in media containing much lower serum concentrations and increased survival periods after serum withdrawal were observed for KD clones. DNA microarray and quantitative polymerase chain reaction screening for differentially expressed genes between KD clones and non-KD control cells revealed significant up-regulation of the tyrosine kinase receptor, KIT, hyperactive mutations of which are often found in AML. Treatment of KD clones with ISCK03, a KIT-specific inhibitor, eliminated the increased survival of KD clones in the absence of serum. Conclusions We suggest that CCDC26 controls growth of myeloid leukemia cells through regulation of KIT expression. A KIT inhibitor might be an effective treatment against the forms of AML in which CCDC26 is altered.