Systematic review of comparative transcriptomic studies of cellular resistance to genotoxic stress

Z B Ismailov; E S Belykh; A A Chernykh; A M Udoratina; D V Kazakov; A V Rybak; S N Kerimova; I O Velegzhaninov

doi:10.1016/j.mrrev.2023.108467

Systematic review of comparative transcriptomic studies of cellular resistance to genotoxic stress

Mutat Res Rev Mutat Res. 2023 Jul-Dec:792:108467. doi: 10.1016/j.mrrev.2023.108467. Epub 2023 Aug 30.

Authors

Z B Ismailov¹, E S Belykh¹, A A Chernykh², A M Udoratina³, D V Kazakov⁴, A V Rybak¹, S N Kerimova⁵, I O Velegzhaninov⁶

Affiliations

¹ Institute of Biology of Komi Science Centre of the Ural Branch of the Russian Academy of Sciences, 28b Kommunisticheskaya St., Syktyvkar 167982, Russia.
² Institute of Physiology of Komi Science Centre of the Ural Branch of the Russian Academy of Sciences, 50 Pervomaiskaya St., Syktyvkar 167982, Russia.
³ Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Avenue, Nizhny Novgorod 603022, Russia.
⁴ Institute of Physics and Mathematics of Komi Science Centre of the Ural Branch of the Russian Academy of Sciences, 4 Oplesnina St., Syktyvkar 167982, Russia.
⁵ State Medical Institution Komi Republican Oncology Center, 46 Nyuvchimskoe highway, Syktyvkar 167904, Russia.
⁶ Institute of Biology of Komi Science Centre of the Ural Branch of the Russian Academy of Sciences, 28b Kommunisticheskaya St., Syktyvkar 167982, Russia. Electronic address: vellio@yandex.ru.

PMID: 37657754
DOI: 10.1016/j.mrrev.2023.108467

Abstract

The development of resistance by tumor cells to various types of therapy is a significant problem that decreases the effectiveness of oncology treatments. For more than two decades, comparative transcriptomic studies of tumor cells with different sensitivities to ionizing radiation and chemotherapeutic agents have been conducted in order to identify the causes and mechanisms underlying this phenomenon. However, the results of such studies have little in common and often contradict each other. We have assumed that a systematic analysis of a large number of such studies will provide new knowledge about the mechanisms of development of therapeutic resistance in tumor cells. Our comparison of 123 differentially expressed gene (DEG) lists published in 98 papers suggests a very low degree of consistency between the study results. Grouping the data by type of genotoxic agent and tumor type did not increase the similarity. The most frequently overexpressed genes were found to be those encoding the transport protein ABCB1 and the antiviral defense protein IFITM1. We put forward a hypothesis that the role played by the overexpression of the latter in the development of resistance may be associated not only with the stimulation of proliferation, but also with the limitation of exosomal communication and, as a result, with a decrease in the bystander effect. Among down regulated DEGs, BNIP3 was observed most frequently. The expression of BNIP3, together with BNIP3L, is often suppressed in cells resistant to non-platinum genotoxic chemotherapeutic agents, whereas it is increased in cells resistant to ionizing radiation. These observations are likely to be mediated by the binary effects of these gene products on survival, and regulation of apoptosis and autophagy. The combined data also show that even such obvious mechanisms as inhibition of apoptosis and increase of proliferation are not universal but show multidirectional changes.

Keywords: Differentially expressed genes; Exosomal communication; Genotoxic stress; Transcriptomes; Tumor resistance.

Publication types

Systematic Review
Review

MeSH terms

Apoptosis / genetics
DNA Damage / genetics
Gene Expression Profiling*
Humans
RNA
Transcriptome* / genetics

Substances

RNA