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.
吸烟是多种恶性肿瘤的明确危险因素，其中最为人熟知的是肺癌。尽管已知多种分子相互作用将烟草烟雾暴露与肺癌联系起来，但关于吸烟对肺癌发生发展、肿瘤进展及治疗反应影响的新数据仍在不断涌现。本研究进一步详细揭示了吸烟与肺鳞状细胞癌中hsa-mir-301a活性之间既已确立的关联。通过运用多种生物信息学工具，我们确定IRF1是肺鳞癌中受吸烟调控的hsa-mir-301a关键靶点。利用临床肺鳞癌组织样本及完整肺组织样本，我们通过实验进一步验证了这一关系。研究显示，在肺鳞癌肿瘤样本中hsa-mir-301a水平升高，IRF1 mRNA水平降低，且两者呈负相关。针对该机制可能影响通路的进一步生物信息学分析表明，IRF1在调控肺鳞癌抗肿瘤免疫应答中具有多面性作用。研究证实IRF1可影响肿瘤免疫浸润、免疫检查点分子表达及免疫检查点阻断疗法的疗效。由此，我们提出一个受吸烟调控的mir301a/IRF1分子轴，该轴可能调控肺鳞癌的抗肿瘤免疫应答及免疫治疗效果，为未来研究开辟了新方向。
肿瘤(癌症)患者之家