在白血病細胞中發現的長鏈非編碼RNA（lncRNA）或許會影響酪氨酸激酶靶向白血病療法的療效，而目前lncRNA CCDC26的功能並沒有被完全解析，而來自廣島大學的研究者則在雜誌Molecular Cancer上刊登了他們的最新研究成果，研究者在文章中揭示了CCDC26控製受體酪氨酸激酶KIT表達的機製，相關研究結果或為理解白血病的複發且幫助開發白血病療法提供一定的幫助。

　　近來轉錄組學的相關研究發現了相對較長但並未轉錄翻譯成為蛋白的大量RNAs，其中lncRNA被認為可以調節其它基因的表達，而機體中lncRNAs的突變或失衡往往會引發一係列疾病，比如癌症，然而lncRNAs的分子功能目前尚未被闡明。

　　研究者Tetsuo Hirano表示，我們發現細胞中名為lncRNA CCDC26的基因的敲除會明顯上調KIT基因的表達，而KIT基因的過度表達則在急性髓性白血病中被發現；研究者發現CCDC26的轉錄在人類髓樣白血病細胞係的細胞核碎片中處於較高的水平，同時CCDC26的敲除會誘發CCDC26 包含內含子的轉錄物的抑製，進而導致轉錄基因被抑製。CCDC26敲除的白血病細胞往往在血清剝除後的生存期會延長，而KIT特殊的抑製劑則會逆轉細胞生存期的延長。

　　最後研究者表示，CCDC26可以通過調節KIT基因的表達來控製髓樣白血病細胞的生長，異常的CCDC26 RNA結構會調整KIT的表達從而誘導意想不到的基因表達；因此以CCDC26拷貝數突變為主要特性的白血病或許可以通過靶向作用KIT的療法來進行治療。

　　doi:10.1186/s12943-015-0364-7

　　PMC:

　　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.