Qin Anqi, Chen Hao, Xu Fan, Li Wenting, Guo Shuai, Zhang Ge, Zhang Aihong, Zheng Aihua, Tian Feng, Zheng Quanhui
Hebei Key Laboratory for Chronic Diseases, Tangshan Key Laboratory for Preclinical and Basic Research On Chronic Diseases, School of Basic Medical Sciences, North China University of Science and Technology, Tangshan, 063210, People's Republic of China.
Department of Laboratory Animal Science, Health Science Center, Peking University, Beijing, 100083, People's Republic of China.
Sci Rep. 2025 Apr 15;15(1):12988. doi: 10.1038/s41598-025-97556-5.
Lung cancer is the second most common cancer in the world. Myeloid-derived suppressor cells (MDSCs) are important cell populations in the microenvironment of lung cancer, which affects the development and treatment of lung cancer. A large number of studies have shown that miRNA can regulate MDSCs, promoting tumor development. Here we aim to explore the role of miR- 150 on MDSCs in lung tumors. We established lung tumor models by injecting miR- 150 knock-out (miR- 150 KO) mice with LLC subcutaneously. MiR- 150 deletion promoted tumor growth and increased the ratio of MDSCs in tumors. In addition, knockdown of miR- 150 resulted in high serum levels of IL- 6 and G-CSF and promoted the expression of suppressive-associated molecules in MDSCs. In vitro, inhibition of miR- 150 led to increased expression of ROS, IRE1α and P-STAT3 in MDSCs. In vivo administration of STAT3 inhibitor significantly inhibited tumor growth in miR- 150 KO mice and reduced ROS level in tumor MDSCs. Our results indicated that miR- 150 deletion promotes lung tumor growth by upregulating P-STAT3 and ROS in MDSCs, suggesting that STAT3 inhibitors are effective in blocking the production of ROS in MDSCs lacking miR- 150.
肺癌是全球第二大常见癌症。髓系来源的抑制性细胞（MDSCs）是肺癌微环境中的重要细胞群体，影响肺癌的发展和治疗。大量研究表明，miRNA可调节MDSCs，促进肿瘤发展。在此，我们旨在探讨miR-150在肺肿瘤中对MDSCs的作用。我们通过皮下注射LLC至miR-150基因敲除（miR-150 KO）小鼠建立肺肿瘤模型。miR-150缺失促进肿瘤生长，并增加肿瘤中MDSCs的比例。此外，敲低miR-150导致血清中IL-6和G-CSF水平升高，并促进MDSCs中抑制相关分子的表达。在体外，抑制miR-150导致MDSCs中ROS、IRE1α和P-STAT3的表达增加。在体内给予STAT3抑制剂可显著抑制miR-150 KO小鼠肿瘤生长，并降低肿瘤MDSCs中的ROS水平。我们的结果表明，miR-150缺失通过上调MDSCs中的P-STAT3和ROS促进肺肿瘤生长，提示STAT3抑制剂可有效阻断缺乏miR-150的MDSCs中ROS的产生。
