Department of Pediatric Oncology and Hematology, Erasmus MC/Sophia Children's Hospital, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Leukemia. 2014 May;28(5):1008-14. doi: 10.1038/leu.2013.308. Epub 2013 Oct 23.
Among the microRNAs (miRNAs) that control different cellular processes, miR-24, miR-126 and miR-365 were shown to regulate cell cycle progression and apoptosis in various types of tumors. Interestingly, these three miRNAs were downregulated in pediatric TCF3-rearranged B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Here, we showed that individual or combined overexpression of miR-24, miR-126 and miR-365 can neither alter the cell cycle progression nor the amount of apoptosis in 697, KASUMI-2 or MHH-CALL-3 TCF3-rearranged leukemic cells. We further integrated the miRNA-mRNA expression data of 37 children with BCP-ALL to identify candidate target genes for these three miRNAs. However, the expression levels of selected candidate target genes (ELL, EBF3 and IRF4 for miR-24, PITPNC1 for miR-126 and ZAP-70 for miR-365) did not reduce upon miRNAs overexpression in MHH-CALL-3 TCF3-rearranged leukemic cells. Although the expression level of AURKB-a validated target for miR-24-was reduced upon miR-24 overexpression in hepatocarcinoma HEP-G2 cells, overexpression of miR-24 cannot alter AURKB expression levels in MHH-CALL-3 TCF3-rearranged leukemic cells. Taken together, our data suggest that miRNAs' function is highly tissue-dependent and that a defined biological target gene or function of one miRNA in a specific tissue cannot be extended as a generalized target/function for that miRNA in all types of cells/tissues.
在调控不同细胞过程的 microRNAs(miRNAs)中,miR-24、miR-126 和 miR-365 被证明可以调控多种类型肿瘤的细胞周期进程和细胞凋亡。有趣的是,这三种 miRNAs 在小儿 TCF3 重排的 B 细胞前体急性淋巴细胞白血病(BCP-ALL)中下调。在这里,我们表明,miR-24、miR-126 和 miR-365 的单独或联合过表达既不能改变 697、KASUMI-2 或 MHH-CALL-3 TCF3 重排白血病细胞的细胞周期进程,也不能增加细胞凋亡的数量。我们进一步整合了 37 名 BCP-ALL 患儿的 miRNA-mRNA 表达数据,以鉴定这三种 miRNAs 的候选靶基因。然而,在 MHH-CALL-3 TCF3 重排白血病细胞中,选定候选靶基因(miR-24 的 ELL、EBF3 和 IRF4,miR-126 的 PITPNC1 和 miR-365 的 ZAP-70)的表达水平并没有因 miRNAs 的过表达而降低。虽然 AURKB(miR-24 的一个验证靶基因)的表达水平在肝癌 HEP-G2 细胞中因 miR-24 的过表达而降低,但 miR-24 的过表达不能改变 MHH-CALL-3 TCF3 重排白血病细胞中 AURKB 的表达水平。总之,我们的数据表明,miRNAs 的功能高度依赖于组织,一种 miRNA 在特定组织中的特定生物学靶基因或功能不能被推广为该 miRNA 在所有类型的细胞/组织中的通用靶基因/功能。