RNA-Seq profiling of deregulated miRs in CLL and their impact on clinical outcome

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.

Inside the chronic lymphocytic leukemia cell: miRNA and chromosomal aberrations

“…It is now possible to use next-generation sequencing (NGS) as an extensive study to search for miRNA molecules that can serve as prognostic and predictive factors in CLL. Kaur et al ( 50 ) conducted a genome-wide small RNA sequencing study to reveal a unique pattern of differential regulation of eight miRNAs in CLL. Upregulated miRNAs include miR-1295a, miR-155 and miR-4524a; while miR-30a, miR-423, miR-486*, let-7e and miR-744 are downregulated ( 50 ).…”

“…Kaur et al ( 50 ) conducted a genome-wide small RNA sequencing study to reveal a unique pattern of differential regulation of eight miRNAs in CLL. Upregulated miRNAs include miR-1295a, miR-155 and miR-4524a; while miR-30a, miR-423, miR-486*, let-7e and miR-744 are downregulated ( 50 ). This demonstrated that miR-4524a and miR-744 are significantly associated with CLL risk and time to first treatment ( 50 ).…”

“…Upregulated miRNAs include miR-1295a, miR-155 and miR-4524a; while miR-30a, miR-423, miR-486*, let-7e and miR-744 are downregulated ( 50 ). This demonstrated that miR-4524a and miR-744 are significantly associated with CLL risk and time to first treatment ( 50 ). These authors also validated NGS results using RT-qPCR.…”

MiR-744 facilitates non-small cell lung cancer progression by direct transcriptional regulation and indirect MAPK pathway activation mediated upregulation of C-FOS

“…Up to now, it has been observed that miR-744 was a promising tumor molecular marker in some tumor tissues or serum (Table 1), including chronic lymphocytic leukemia [8], hepatocellular carcinoma [12], osarcoteosma [18] and gastric cancer [31]. However, there is still no study on the expression of miR-744 in lung cancer.…”

Higher Physical Fitness Regulates In Vitro Tumor Cell Growth in Older Adults with Treatment Naïve Chronic Lymphocytic Leukemia (CLL)

“…The role of both intracellular and extracellular (i.e. cell free and packaged in extracellular vesicles) miRNAs in CLL have revealed at least 10-20 miRNAs associated with varying disease characteristics [51][52][53][54][55][56][57]. Exosomes are the smallest known extracellular vesicles (50-100 nm) with distinct biochemical properties that carry cellular components, such as proteins, peptides, lipids, mRNA, and miRNAs [58].…”