Kyriakidis Ioannis, Kyriakidis Konstantinos, Tsezou Aspasia
Laboratory of Cytogenetics and Molecular Genetics, Faculty of Medicine, School of Health Sciences, University of Thessaly, 41500 Larissa, Greece.
Laboratory of Biological Chemistry, School of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.
Cancers (Basel). 2022 Aug 17;14(16):3976. doi: 10.3390/cancers14163976.
MicroRNAs (miRNAs) have been implicated in childhood acute lymphoblastic leukemia (ALL) pathogenesis. We performed a systematic review and meta-analysis of miRNA single-nucleotide polymorphisms (SNPs) in childhood ALL compared with healthy children, which revealed (i) that the CC genotype of rs4938723 in pri-miR-34b/c and the TT genotype of rs543412 in miR-100 confer protection against ALL occurrence in children; (ii) no significant association between rs2910164 genotypes in miR-146a and childhood ALL; and (iii) SNPs in DROSHA, miR-449b, miR-938, miR-3117 and miR-3689d-2 genes seem to be associated with susceptibility to B-ALL in childhood. A review of published literature on differential expression of miRNAs in children with ALL compared with controls revealed a significant upregulation of the miR-128 family, miR-130b, miR-155, miR-181 family, miR-210, miR-222, miR-363 and miR-708, along with significant downregulation of miR-143 and miR-148a, seem to have a definite role in childhood ALL development. MicroRNA signatures among childhood ALL subtypes, along with differential miRNA expression patterns between B-ALL and T-ALL cases, were scrutinized. With respect to T-ALL pediatric cases, we reanalyzed RNA-seq datasets with a robust and sensitive pipeline and confirmed the significant differential expression of hsa-miR-16-5p, hsa-miR-19b-3p, hsa-miR-92a-2-5p, hsa-miR-128-3p (ranked first), hsa-miR-130b-3p and -5p, hsa-miR-181a-5p, -2-3p and -3p, hsa-miR-181b-5p and -3p, hsa-miR-145-5p and hsa-miR-574-3p, as described in the literature, along with novel identified miRNAs.
微小RNA（miRNA）与儿童急性淋巴细胞白血病（ALL）的发病机制有关。我们对儿童ALL患者与健康儿童的miRNA单核苷酸多态性（SNP）进行了系统综述和荟萃分析，结果显示：（i）pri-miR-34b/c中rs4938723的CC基因型和miR-100中rs543412的TT基因型可保护儿童预防ALL的发生；（ii）miR-146a中rs2910164基因型与儿童ALL之间无显著关联；（iii）DROSHA、miR-449b、miR-938、miR-3117和miR-3689d-2基因中的SNP似乎与儿童B-ALL易感性相关。对已发表的关于ALL儿童与对照儿童miRNA差异表达的文献综述显示，miR-128家族、miR-130b、miR-155、miR-181家族、miR-210、miR-222、miR-363和miR-708显著上调，同时miR-143和miR-148a显著下调，这似乎在儿童ALL发展中起明确作用。对儿童ALL亚型中的miRNA特征以及B-ALL和T-ALL病例之间不同的miRNA表达模式进行了仔细研究。对于儿童T-ALL病例，我们使用强大且灵敏的流程重新分析了RNA测序数据集，并确认了文献中所述的hsa-miR-16-5p、hsa-miR-19b-3p、hsa-miR-92a-2-5p、hsa-miR-128-3p（排名第一）、hsa-miR-130b-3p和-5p、hsa-miR-181a-5p、-2-3p和-3p、hsa-miR-181b-5p和-3p、hsa-miR-145-5p和hsa-miR-574-3p的显著差异表达，以及新发现的miRNA。
