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Comprehensive DNA Methylation Analysis Using a Methyl-CpG-binding Domain Capture-based Method in Chronic Lymphocytic Leukemia Patients
Published on: June 16, 2017
RNA-Seq profiling of deregulated miRs in CLL and their impact on clinical outcome
Gurvinder Kaur1, Vivek Ruhela2, Lata Rani1
1Laboratory Oncology Unit, Dr. B.R.A.IRCH, All India Institute of Medical Sciences, New Delhi, India.
Abstract:
Abnormal expression patterns of regulatory small non-coding RNA (sncRNA) molecules such as microRNAs (miRs), piwi-interacting RNAs (piRNAs), and small nucleolar RNAs (snoRNAs) play an important role in the development and progression of cancer. Identification of clinically relevant sncRNA signatures could, therefore, be of tremendous translational value. In the present study, genome-wide small RNA sequencing identified a unique pattern of differential regulation of eight miRs in Chronic Lymphocytic Leukemia (CLL). Among these, three were up-regulated (miR-1295a, miR-155, miR-4524a) and five were down-regulated (miR-30a, miR-423, miR-486*, let-7e, and miR-744) in CLL. Altered expression of all these eight differentially expressed miRs (DEMs) was validated by RQ-PCR. Besides, seven novel sequences identified to have elevated expression levels in CLL turned out to be transfer RNA (tRNA)/piRNAs (piRNA-30799, piRNA-36225)/snoRNA (SNORD43) related. Multivariate analysis showed that miR-4524a (HR: 1.916, 95% CI: 1.080-3.4, p value: 0.026) and miR-744 (HR: 0.415, 95% CI: 0.224-0.769, p value: 0.005) were significantly associated with risk and time to first treatment. Further investigations could help establish the scope of integration of these DEM markers into risk stratification designs and prognostication approaches for CLL.
Insights
Small non-coding RNAs (sncRNAs) like microRNAs (miRs) are crucial in cancer. Researchers identified eight differentially expressed miRs in Chronic Lymphocytic Leukemia (CLL), with two showing significant association with patient risk and treatment time.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Aberrant expression of small non-coding RNAs (sncRNAs), including microRNAs (miRs), piwi-interacting RNAs (piRNAs), and small nucleolar RNAs (snoRNAs), is implicated in cancer development and progression.
- Identifying specific sncRNA signatures holds significant translational potential for clinical applications in cancer management.
Purpose of the Study:
- To identify novel small non-coding RNA (sncRNA) signatures associated with Chronic Lymphocytic Leukemia (CLL).
- To investigate the potential of these sncRNAs as biomarkers for risk stratification and prognostication in CLL patients.
Main Methods:
- Genome-wide small RNA sequencing was employed to profile sncRNA expression in CLL.
- Differential expression analysis identified eight microRNAs (miRs) with altered expression patterns.
- Quantitative reverse transcription PCR (RQ-PCR) was used to validate the expression levels of differentially expressed miRs (DEMs).
- Novel transfer RNA (tRNA)/piRNA/snoRNA related sequences were also identified.
Main Results:
- A unique pattern of eight differentially expressed miRs was identified in CLL, with three up-regulated and five down-regulated.
- Validation confirmed the altered expression of these eight miRs.
- Seven novel tRNA/piRNA/snoRNA related sequences showed elevated expression in CLL.
- Multivariate analysis revealed that miR-4524a and miR-744 were significantly associated with patient risk and time to first treatment.
Conclusions:
- The study identified a distinct set of differentially expressed microRNAs (miRs) and other small non-coding RNAs (sncRNAs) in Chronic Lymphocytic Leukemia (CLL).
- Specific miRs, namely miR-4524a and miR-744, demonstrate prognostic value, correlating with patient risk and treatment initiation.
- These findings suggest the potential utility of these sncRNAs as biomarkers for improving risk stratification and prognostication in CLL.
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