TY - JOUR

T1 - Roles of Interferon Regulatory Factor 1 in Tumor Progression and Regression: Two Sides of a Coin

AU - Perevalova, Alina M.

AU - Gulyaeva, Lyudmila F.

AU - Pustylnyak, Vladimir O.

N1 - This research was funded by the RUSSIAN SCIENCE FOUNDATION, grant number 22-15-00065.

PY - 2024/2

Y1 - 2024/2

N2 - IRF1 is a transcription factor well known for its role in IFN signaling. Although IRF1 was initially identified for its involvement in inflammatory processes, there is now evidence that it provides a function in carcinogenesis as well. IRF1 has been shown to affect several important antitumor mechanisms, such as induction of apoptosis, cell cycle arrest, remodeling of tumor immune microenvironment, suppression of telomerase activity, suppression of angiogenesis and others. Nevertheless, the opposite effects of IRF1 on tumor growth have also been demonstrated. In particular, the “immune checkpoint” molecule PD-L1, which is responsible for tumor immune evasion, has IRF1 as a major transcriptional regulator. These and several other properties of IRF1, including its proposed association with response and resistance to immunotherapy and several chemotherapeutic drugs, make it a promising object for further research. Numerous mechanisms of IRF1 regulation in cancer have been identified, including genetic, epigenetic, transcriptional, post-transcriptional, and post-translational mechanisms, although their significance for tumor progression remains to be explored. This review will focus on the established tumor-suppressive and tumor-promoting functions of IRF1, as well as the molecular mechanisms of IRF1 regulation identified in various cancers.

AB - IRF1 is a transcription factor well known for its role in IFN signaling. Although IRF1 was initially identified for its involvement in inflammatory processes, there is now evidence that it provides a function in carcinogenesis as well. IRF1 has been shown to affect several important antitumor mechanisms, such as induction of apoptosis, cell cycle arrest, remodeling of tumor immune microenvironment, suppression of telomerase activity, suppression of angiogenesis and others. Nevertheless, the opposite effects of IRF1 on tumor growth have also been demonstrated. In particular, the “immune checkpoint” molecule PD-L1, which is responsible for tumor immune evasion, has IRF1 as a major transcriptional regulator. These and several other properties of IRF1, including its proposed association with response and resistance to immunotherapy and several chemotherapeutic drugs, make it a promising object for further research. Numerous mechanisms of IRF1 regulation in cancer have been identified, including genetic, epigenetic, transcriptional, post-transcriptional, and post-translational mechanisms, although their significance for tumor progression remains to be explored. This review will focus on the established tumor-suppressive and tumor-promoting functions of IRF1, as well as the molecular mechanisms of IRF1 regulation identified in various cancers.

KW - IRF1

KW - cancer

KW - immunotherapy

KW - interferon

KW - Signal Transduction

KW - Humans

KW - Tumor Microenvironment

KW - Neoplasms/genetics

KW - Carcinogenesis/genetics

KW - Interferon Regulatory Factor-1/genetics

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85185855671&origin=inward&txGid=d811f1e5e30ac3bfcc9fad35f7d9a7ef

UR - https://www.webofscience.com/wos/woscc/full-record/WOS:001168362200001

UR - https://www.mendeley.com/catalogue/d3f94c8f-6863-3691-b7ed-0cb67be71db3/

U2 - 10.3390/ijms25042153

DO - 10.3390/ijms25042153

M3 - Article

C2 - 38396830

VL - 25

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 4

M1 - 2153

ER -