Expression of circulating miRNAs associated with lymphocyte differentiation and activation in CLL—another piece in the puzzle

Abstract

Expression of microRNAs is altered in cancer. Circulating miRNA level assessed in body fluids commonly reflects their expression in tumor cells. In leukemias, however, both leukemic and nonleukemic cells compose circulating miRNA expression profile of peripheral blood. The latter contribution to extracellular miRNA pool may result in specific microenvironmental signaling, which promotes proliferation and survival. In our study, we used qT-PCR to assay peripheral blood serum of 22 chronic lymphocytic leukemia (CLL) patients for the expression of 84 miRNAs associated with activation and differentiation of B and T lymphocytes. Results were analyzed regarding the most important prognostic factors. We have found that the general expression of examined miRNAs in CLL patients was lower as compared to healthy volunteers. Only miR-34a-5p, miR31-5p, miR-155-5p, miR-150-5p, miR-15a-3p, and miR-29a-3p were expressed on a higher level. Alterations of expression observed in CLL patients involved miRNAs associated both with B and T lymphocyte differentiation and activation. The most important discriminating factors for all functional miRNA groups were trisomy 12, CD38 expression, B2M level, WBC, and NOTCH1 gene mutation. Correlation of expression of miRNAs related to T lymphocytes with prognostic factors proves their supportive function in a leukemic microenvironment. Further studies utilizing a larger test group of patients may warrant the identification of circulating miRNAs that are key players in intercellular interactions and should be considered in the design of microenvironment-targeted therapies.Electronic supplementary materialThe online version of this article (doi:10.1007/s00277-016-2840-6) contains supplementary material, which is available to authorized users.

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

“…Hsa-let-7e is yet another important miR that was downregulated in CLL in this study and has been implicated in several cancers. Similar studies on CLL such as by Filip et al 29 have also reported lower expression of let-7e in CLL as well as poor prognostic CD38 + CLL subgroup, which further supports observations of this study. Incidentally, three of the eight DEMs observed in this study, namely miR-423, miR-4524a and miR-744 are located on chromosome 17.…”

“…The miRNA profiling in this study has identified differential regulation of eight important known miRs and seven novel sncRNA species related to tRNA, piRNA, and snoRNA that might contribute to the development/progression of CLL by targeting various crucial genes. Of the 8 known miRs, differential regulation of four miRNAs i.e., miR-155 7-9 , miR-486-5p 28 , miR-423 29 and hsa-let-7e 29 has been earlier reported in CLL. miR-30a which has been shown to have tumor suppressor role in lung cancer 30 and breast cancer 31 was found to be down-regulated in the present study.…”

“…In this study, expression levels of miR-423 were found to be reduced in CLL. A qRT-PCR based study has also reported reduced expression of miR-423 in CLL patients particularly in the context of higher lactate dehydrogenase (LDH) activity 29 . Higher expression of miR-744 among older female patients with ovarian carcinoma has been reported to correlate with prolonged disease free survival, suggesting its protective influence 39 .…”

Cell‐to‐cell communication: microRNAs as hormones

“…Finally, Filip et al . (2017) showed that miR‐34a‐5p, miR31‐5p, miR‐155‐5p, miR‐150‐5p, miR‐15a‐3p, and miR‐29a‐3p were upregulated in serum samples of CLL patients compared with healthy individuals.…”

“…In addition, circulating miR-192 has been found to be significantly downregulated in patients with chronic lymphocytic leukemia (CLL) compared with healthy individuals (Fathullahzadeh et al, 2016). Finally, Filip et al (2017) showed that miR-34a-5p, miR31-5p, miR-155-5p, miR-150-5p, miR-15a-3p, and miR-29a-3p were upregulated in serum samples of CLL patients compared with healthy individuals.…”