Deficiency of miR-155 in leukemic B-cells results in cell cycle arrest and deregulation of MIR155HG/TP53INP1/CDKN1A/CCND1 network
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389030%3A_____%2F25%3A00604361" target="_blank" >RIV/61389030:_____/25:00604361 - isvavai.cz</a>
Result on the web
<a href="https://doi.org/10.1016/j.arcmed.2024.103124" target="_blank" >https://doi.org/10.1016/j.arcmed.2024.103124</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.arcmed.2024.103124" target="_blank" >10.1016/j.arcmed.2024.103124</a>
Alternative languages
Result language
angličtina
Original language name
Deficiency of miR-155 in leukemic B-cells results in cell cycle arrest and deregulation of MIR155HG/TP53INP1/CDKN1A/CCND1 network
Original language description
Background. Cell cycle progression and leukemia development are tightly regulated processes in which even a small imbalance in the expression of cell cycle regulatory molecules and microRNAs (miRNAs) can lead to an increased risk of cancer/leukemia development. Here, we focus on the study of a ubiquitous, multifunctional, and oncogenic miRNA-hsa-miR-155-5p (miR-155, MIR155HG), which is overexpressed in malignancies including chronic lymphocytic leukemia (CLL). Nonetheless, the precise mechanism of how miR-155 regulates the cell cycle in leukemic cells remains the subject of extensive research. Methods. We edited the CLL cell line MEC-1 by CRISPR/Cas9 to introduce a short deletion within the MIR155HG gene. To describe changes at the transcriptome and miRNome level in miR-155-deficient cells, we performed mRNA-seq/miRNA-seq and validated changes by qRT-PCR. Flow cytometry was used to measure cell cycle kinetics. A WST-1 assay, hemocytometer, and Annexin V/PI staining assessed cell viability and proliferation. Results. The limited but phenotypically robust miR-155 modification impaired cell proliferation, cell cycle, and cell ploidy. This was accompanied by overexpression of the negative cell cycle regulator p21/CDKN1A and Cyclin D1 ( CCND1 ). We confirmed the overexpression of canonical miR-155 targets such as PU.1, FOS, SHIP-1, TP53INP1 and revealed new potential targets ( FCRL5, ISG15, and MX1). Conclusions. We demonstrate that miR-155 deficiency impairs cell proliferation, cell cycle, transcriptome, and miRNome via deregulation of the MIR155HG/TP53INP1/CDKN1A/CCND1 axis. Our CLL model is valuable for further studies to manipulate miRNA levels to revert highly aggressive leukemic cells to nearly benign or non-leukemic types.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30205 - Hematology
Result continuities
Project
<a href="/en/project/LM2023050" target="_blank" >LM2023050: National Infrastructure for Biological and Medical Imaging</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Archives of Medical Research
ISSN
0188-4409
e-ISSN
1873-5487
Volume of the periodical
56
Issue of the periodical within the volume
3
Country of publishing house
US - UNITED STATES
Number of pages
19
Pages from-to
103124
UT code for WoS article
001367920100001
EID of the result in the Scopus database
2-s2.0-85210031723