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Updated: Jun 4, 2026
Comprehensive DNA Methylation Analysis Using a Methyl-CpG-binding Domain Capture-based Method in Chronic Lymphocytic Leukemia Patients
Published on: June 16, 2017
Integrative analysis of next generation sequencing for small non-coding RNAs and transcriptional regulation in
Dominik Beck1, Steve Ayers, Jianguo Wen
1Bioengineering and Bioinformatics Program, Department of Pathology, The Methodist Hospital Research Institute, Weill Cornell Medical College, Houston, TX, 77030, USA.
Background:
Myelodysplastic Syndromes (MDSS) are pre-leukemic disorders with increasing incident rates worldwide, but very limited treatment options. Little is known about small regulatory RNAs and how they contribute to pathogenesis, progression and transcriptome changes in MDS.
Methods:
Patients' primary marrow cells were screened for short RNAs (RNA-seq) using next generation sequencing. Exon arrays from the same cells were used to profile gene expression and additional measures on 98 patients obtained. Integrative bioinformatics algorithms were proposed, and pathway and ontology analysis performed.
Results:
In low-grade MDS, observations implied extensive post-transcriptional regulation via microRNAs (miRNA) and the recently discovered Piwi interacting RNAs (piRNA). Large expression differences were found for MDS-associated and novel miRNAs, including 48 sequences matching to miRNA star (miRNA*) motifs. The detected species were predicted to regulate disease stage specific molecular functions and pathways, including apoptosis and response to DNA damage. In high-grade MDS, results suggested extensive post-translation editing via transfer RNAs (tRNAs), providing a potential link for reduced apoptosis, a hallmark for this disease stage. Bioinformatics analysis confirmed important regulatory roles for MDS linked miRNAs and TFs, and strengthened the biological significance of miRNA*. The "RNA polymerase II promoters" were identified as the tightest controlled biological function. We suggest their control by a miRNA dominated feedback loop, which might be linked to the dramatically different miRNA amounts seen between low and high-grade MDS.
Discussion:
The presented results provide novel findings that build a basis of further investigations of diagnostic biomarkers, targeted therapies and studies on MDS pathogenesis.
Insights
Small regulatory RNAs, including microRNAs (miRNAs) and Piwi interacting RNAs (piRNAs), play key roles in Myelodysplastic Syndromes (MDS) pathogenesis. These findings offer new avenues for MDS diagnostics and therapies.
Area of Science:
- Molecular Biology
- Genomics
- Bioinformatics
Background:
- Myelodysplastic Syndromes (MDS) are pre-leukemic disorders with rising global incidence and limited treatment options.
- The role of small regulatory RNAs in MDS pathogenesis, progression, and transcriptome alteration remains largely unexplored.
Purpose of the Study:
- To investigate the role of small regulatory RNAs in Myelodysplastic Syndromes.
- To identify potential diagnostic biomarkers and therapeutic targets for MDS.
Main Methods:
- Next-generation sequencing (RNA-seq) of short RNAs from patient primary marrow cells.
- Exon arrays for gene expression profiling in 98 MDS patients.
- Integrative bioinformatics, pathway, and ontology analysis.
Main Results:
- Extensive post-transcriptional regulation by microRNAs (miRNAs) and Piwi interacting RNAs (piRNAs) observed in low-grade MDS.
- Identification of novel and differentially expressed miRNAs, including miRNA* sequences, impacting apoptosis and DNA damage response.
- Evidence of post-translational tRNA editing in high-grade MDS, potentially linked to reduced apoptosis; miRNA-dominated feedback loops suggested for RNA polymerase II promoter control.
Conclusions:
- Novel insights into the regulatory roles of small RNAs in MDS pathogenesis.
- Findings support further investigation for diagnostic biomarkers and targeted therapies in MDS.
- The study establishes a foundation for understanding the molecular mechanisms driving MDS progression.
