Abstract
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.
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