Luciano Neila, Coppola Luigi, Salvatore Giuliana, Primo Pasquale, Parasole Rosanna, Mirabelli Peppino, Orlandella Francesca Maria
Department of Medical, Movement and Wellbeing Sciences, University of Naples Parthenope, 80133 Naples, Italy.
CEINGE-Biotecnologie Avanzate "Franco Salvatore", 80131 Naples, Italy.
Genes (Basel). 2025 Mar 31;16(4):420. doi: 10.3390/genes16040420.
Less than 5% of the DNA sequence encodes for proteins, and the remainder encodes for non-coding RNAs (ncRNAs). Among the members of the ncRNA family, microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) play a pivotal role in the insurgence and progression of several cancers, including leukemia. Thought to have different molecular mechanisms, both miRNAs and lncRNAs act as epigenetic factors modulating gene expression and influencing hematopoietic differentiation, proliferation and immune system function. Here, we discuss the most recent findings on the main molecular mechanisms by which miRNAs and lncRNAs are involved in the pathogenesis and progression of pediatric T acute lymphoblastic leukemia (T-ALL), pointing out their potential utility as therapeutic targets and as biomarkers for early diagnosis, risk stratification and prognosis. miRNAs are involved in the pathogenesis of T-ALL, acting both as tumor suppressors and as oncomiRs. By contrast, to the best of our knowledge, the literature highlights lncRNAs as acting only as oncogenes in this type of cancer by inhibiting apoptosis and promoting cell cycle and drug resistance. Additionally, here, we discuss how these molecules could be detected in the plasma of T-ALL patients, highlighting that lncRNAs may represent a new class of promising accurate and sensitive biomarkers in these young patients. Thus, the unveiling of the aberrant signature of circulating and intracellular levels of lncRNAs could have great clinical utility for obtaining a more accurate definition of prognosis and uncovering novel therapeutic strategies against T-ALL in children. However, further investigations are needed to better define the standard methodological procedure for their quantification and to obtain their specific targeting in T-ALL pediatric patients.
不到5%的DNA序列编码蛋白质,其余部分编码非编码RNA(ncRNA)。在ncRNA家族成员中,微小RNA(miRNA)和长链非编码RNA(lncRNA)在包括白血病在内的几种癌症的发生和发展中起关键作用。尽管miRNA和lncRNA被认为具有不同的分子机制,但它们都作为表观遗传因子调节基因表达,并影响造血分化、增殖和免疫系统功能。在此,我们讨论了关于miRNA和lncRNA参与儿童T细胞急性淋巴细胞白血病(T-ALL)发病机制和进展的主要分子机制的最新研究结果,指出它们作为治疗靶点以及早期诊断、风险分层和预后生物标志物的潜在用途。miRNA参与T-ALL的发病机制,既作为肿瘤抑制因子,也作为致癌miRNA。相比之下,据我们所知,文献强调lncRNA在这类癌症中仅作为癌基因发挥作用,通过抑制细胞凋亡、促进细胞周期进展和产生耐药性。此外,我们在此讨论了如何在T-ALL患者的血浆中检测这些分子,强调lncRNA可能代表这类年轻患者中一类有前景的新型准确且敏感的生物标志物。因此,揭示循环和细胞内lncRNA水平的异常特征对于更准确地定义预后以及发现针对儿童T-ALL的新治疗策略可能具有重大临床意义。然而,需要进一步研究以更好地确定其定量的标准方法程序,并在儿童T-ALL患者中实现对它们的特异性靶向作用。