TY - JOUR

T1 - Smoking-Mediated miR-301a/IRF1 Axis Controlling Immunotherapy Response in Lung Squamous Cell Carcinoma Revealed by Bioinformatic Analysis

AU - Perevalova, Alina M.

AU - Kononchuk, Vladislav V.

AU - Kalinina, Tatiana S.

AU - Kozlov, Vadim V.

AU - Gulyaeva, Lyudmila F.

AU - Pustylnyak, Vladimir O.

N1 - The authors acknowledge the Center for Collective Use \u201CProteomic Analysis\u201D (supported by funding from the Ministry of Science and Higher Education of the Russian Federation, Agreement No. 075-15-2021-691) for providing the necessary equipment to perform this study. We also thank our colleagues for their support. This research was funded by the Russian Science Foundation, grant number 22-15-00065.

PY - 2024/6

Y1 - 2024/6

N2 - Smoking is an established risk factor for a variety of malignant tumors, the most well-known of which is lung cancer. Various molecular interactions are known to link tobacco smoke exposure to lung cancer, but new data are still emerging on the effects of smoking on lung cancer development, progression, and tumor response to therapy. In this study, we reveal in further detail the previously established association between smoking and hsa-mir-301a activity in lung squamous cell carcinoma, LUSC. Using different bioinformatic tools, we identified IRF1 as a key smoking-regulated target of hsa-mir-301a in LUSC. We further confirmed this relationship experimentally using clinical LUSC tissue samples and intact lung tissue samples. Thus, increased hsa-mir-301a levels, decreased IRF1 mRNA levels, and their negative correlation were shown in LUSC tumor samples. Additional bioinformatic investigation for potential pathways impacted by such a mechanism demonstrated IRF1’s multifaceted role in controlling the antitumor immune response in LUSC. IRF1 was then shown to affect tumor immune infiltration, the expression of immune checkpoint molecules, and the efficacy of immune checkpoint blockade therapy. As a result, here we suggest a smoking-regulated mir301a/IRF1 molecular axis that could modulate the antitumor immune response and immunotherapy efficacy in LUSC, opening up novel opportunities for future research.

AB - Smoking is an established risk factor for a variety of malignant tumors, the most well-known of which is lung cancer. Various molecular interactions are known to link tobacco smoke exposure to lung cancer, but new data are still emerging on the effects of smoking on lung cancer development, progression, and tumor response to therapy. In this study, we reveal in further detail the previously established association between smoking and hsa-mir-301a activity in lung squamous cell carcinoma, LUSC. Using different bioinformatic tools, we identified IRF1 as a key smoking-regulated target of hsa-mir-301a in LUSC. We further confirmed this relationship experimentally using clinical LUSC tissue samples and intact lung tissue samples. Thus, increased hsa-mir-301a levels, decreased IRF1 mRNA levels, and their negative correlation were shown in LUSC tumor samples. Additional bioinformatic investigation for potential pathways impacted by such a mechanism demonstrated IRF1’s multifaceted role in controlling the antitumor immune response in LUSC. IRF1 was then shown to affect tumor immune infiltration, the expression of immune checkpoint molecules, and the efficacy of immune checkpoint blockade therapy. As a result, here we suggest a smoking-regulated mir301a/IRF1 molecular axis that could modulate the antitumor immune response and immunotherapy efficacy in LUSC, opening up novel opportunities for future research.

KW - IRF1

KW - immunotherapy

KW - miR-301a

KW - smoking

KW - squamous cell lung cancer

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85197149084&origin=inward&txGid=f2c98131f09d4d03cf0aced0a9af45fd

UR - https://www.mendeley.com/catalogue/5cfde52d-31a1-3b02-b78d-e40bcdebbb9b/

U2 - 10.3390/cancers16122208

DO - 10.3390/cancers16122208

M3 - Article

C2 - 38927914

VL - 16

JO - Cancers

JF - Cancers

SN - 2072-6694

IS - 12

M1 - 2208

ER -