Abstract 4784
Background
Doxorubicin is an anthracycline antibiotic that acts as a DNA intercalating agent, inhibiting the topoisomerase II and inducing the apoptotic cell death, mainly due to the accumulation of double-strand DNA breaks (DSB). This research aims to identify in what way the abnormalities in microRNA (miRNA) expression profile in cancer cells can confer them the resistance to doxorubicin.
Methods
MiRNA targets within gene transcripts were predicted in silico using the TargetScan software.
Results
Binding sites for miRNAs miR-21, miR-96, miR-183 and miR-365, which are usually upregulated in cancer cells, were revealed in transcript of TOP2A gene encoding topoisomerase II-alpha. Transcripts of proapoptotic genes BID, BCL2L11 (BIM), BMF, BAX, BAK1, PMAIP1 (NOXA), and BBC3 (PUMA) as well as transcripts of tumor suppressor genes TP53 and PTEN carry targets for at least one of hyperexpressed miRNAs miR-19, miR-21, miR-23, miR-27, miR-29, miR-155, miR-181, miR-221/222 and miR-375. Downregulation of anti-onco-miRNAs let-7, miR-22, miR-34, miR-101, miR-125, miR-140, miR-143, miR-199, miR-200, miR-203, miR-204 and miR-205 allows overexpression of antiapoptotic genes BCL2, BCL2L1 (Bcl-XL), MCL1 and AKT1. In the same way, downregulation of the anti-onco-miRNAs can lead to overexpression of ABCA1/4/12, ABCB1 (MDR1), ABCB6, ABCC1 (MRP1) and ABCC3/5/8/11 genes encoding the ATP binding cassette (ABC) transporters. Moreover, multiple targets for the both up- and downregulated miRNAs were found in transcripts of XRCC5/6, PRKDC, LIG4, DCLRE1C, NHEJ1 (XLF), RAD50/51/51B/51D/52/54B/54L, MRE11A, NBN (NBS1), GEN1, ATM and ATR genes encoding the key elements of non-homologous end joining and homologous recombination pathways.
Conclusions
Obviously, in case of doxorubicin administration, strategy of early tumors consists in strengthening of miR-21 expression with the purpose to silence TOP2A gene and escape from immediate apoptotic death. Advanced tumors with more profound abnormalities in miRNA signature overexpress antiapoptotic genes as well as genes responsible for DSB repair and drug efflux and, therefore, can do without the TOP2A silencing.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
3181 - Effects of Three Products in the Prevention and Treatment of Chemotherapy and Radiation Therapy-Induced Oral Mucositis
Presenter: Francesca Zannier
Session: Poster Display session 1
Resources:
Abstract
2433 - Boiling Histotripsy-induced Mechanical Ablation Modulates Tumour Microenvironment by Promoting Immunogenic Cell Death of Cancers
Presenter: Cheol-Hee Shin
Session: Poster Display session 1
Resources:
Abstract
2663 - The bacterial receptor NOD2 mediates LGR5+ intestinal stem cells protection against irradiation via mitophagy activation
Presenter: Antonin Levy
Session: Poster Display session 1
Resources:
Abstract
3213 - Pulse mode irradiation regimen of PDT results in high progression free and overall survival in mice with model tumor
Presenter: Alexey Bogdanov
Session: Poster Display session 1
Resources:
Abstract
3722 - Proton-sensitizing effect of small molecule inhibitor of P300 histone acetyltransferase C646 in human pancreatic cancer cells.
Presenter: Sungwon Shin
Session: Poster Display session 1
Resources:
Abstract
5805 - Red-Blood-Cell-Membrane-Enveloped Magnetic Nanoclusters as a Biomimetic Theranostic Nanoplatform for Bimodal Imaging Guided Cancer Photothermal Therapy
Presenter: sheng wang
Session: Poster Display session 1
Resources:
Abstract
5251 - Urine cell-free and extracellular vesicle cargo miRNAs as biomarkers for prostate cancer diagnosis
Presenter: Ivan Zaporozhchenko
Session: Poster Display session 1
Resources:
Abstract
3657 - Parkin, APEX1 and BCL2L1 Tissue Expression in Southern Brazilian Patients with Different Breast Cancer Molecular Subtypes
Presenter: Bianca Cabral
Session: Poster Display session 1
Resources:
Abstract
2839 - Obesity and prognosis in breast cancer
Presenter: Noha Ibrahim
Session: Poster Display session 1
Resources:
Abstract
5132 - SIPA1 is a modulator of HGF induced tumor metastasis via the regulation of tight junctions in lung adenocarcinoma cells
Presenter: Chang Liu
Session: Poster Display session 1
Resources:
Abstract