Talebi Elham, Ghoraeian Pegah, Shams Zinat, Rahimi Hamzeh
Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
Department of Biological Science, Kharazmi University, Tehran, Iran.
Ann Hematol. 2024 Dec;103(12):5439-5447. doi: 10.1007/s00277-024-05763-3. Epub 2024 Sep 3.
Acute lymphoblastic leukemia (ALL) is a common hematologic cancer with unique incidence and prognosis patterns in people of all ages. Recent molecular biology advances have illuminated ALL's complex molecular pathways, notably the Hedgehog (Hh) signaling system and non-coding RNAs (ncRNAs). This work aimed to unravel the molecular complexities of the link between Hh signaling and ALL by concentrating on long non-coding RNAs (lncRNAs) and their interactions with significant Hh pathway genes.
To analyze differentially expressed lncRNAs and genes in ALL, microarray data from the Gene Expression Omnibus (GEO) was reanalyzed using a systems biology approach. Hh signaling pathway-related genes were identified and their relationship with differentially expressed long non-coding RNAs (DElncRNAs) was analyzed using Pearson's correlation analysis. A regulatory network was built by identifying miRNAs that target Hh signaling pathway-related mRNAs.
193 DEGs and 226 DElncRNAs were found between ALL and normal bone marrow samples. Notably, DEGs associated with the Hh signaling pathway were correlated to 26 DElncRNAs. Later studies showed interesting links between DElncRNAs and biological processes and pathways, including drug resistance, immune system control, and carcinogenic characteristics. DEGs associated with the Hh signaling pathway have miRNAs in common with miRNAs already known to be involved in ALL, including miR-155-5p, and miR-211, highlighting the complexity of the regulatory landscape in this disease.
The complex connections between Hh signaling, lncRNAs, and miRNAs in ALL have been unveiled in this study, indicating that DElncRNAs linked to Hh signaling pathway genes could potentially serve as therapeutic targets and diagnostic biomarkers for ALL.
急性淋巴细胞白血病(ALL)是一种常见的血液系统癌症,在各年龄段人群中具有独特的发病率和预后模式。近期分子生物学进展揭示了ALL复杂的分子途径,尤其是刺猬信号通路(Hh)和非编码RNA(ncRNAs)。这项工作旨在通过关注长链非编码RNA(lncRNAs)及其与重要Hh信号通路基因的相互作用,来阐明Hh信号与ALL之间联系的分子复杂性。
为分析ALL中差异表达的lncRNAs和基因,采用系统生物学方法对来自基因表达综合数据库(GEO)的微阵列数据进行重新分析。鉴定Hh信号通路相关基因,并使用Pearson相关分析分析它们与差异表达的长链非编码RNA(DElncRNAs)的关系。通过鉴定靶向Hh信号通路相关mRNA的miRNA构建调控网络。
在ALL与正常骨髓样本之间发现了193个差异表达基因(DEGs)和226个差异表达lncRNAs(DElncRNAs)。值得注意的是,与Hh信号通路相关的DEGs与26个DElncRNAs相关。后续研究表明DElncRNAs与包括耐药性、免疫系统控制和致癌特征在内的生物学过程及途径之间存在有趣的联系。与Hh信号通路相关的DEGs与已知参与ALL的miRNA(包括miR-155-5p和miR-211)有共同的miRNA,突出了该疾病调控格局的复杂性。
本研究揭示了ALL中Hh信号、lncRNAs和miRNAs之间的复杂联系,表明与Hh信号通路基因相关的DElncRNAs可能作为ALL的治疗靶点和诊断生物标志物。