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Jian-hua Zhou,1,* Zhi-xian Yao,2,* Zhong Zheng,2,* Jun Yang,1 Rui Wang,1 Shi-jie Fu,1 Xu-feng Pan,1 Zhi-hong Liu,2 Ke Wu2 1Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, People’s Republic of China; 2Department of Urology, Shanghai General Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jian-hua Zhou; Ke Wu Email drzhihuazhou@163.com; doctorwuke@sjtu.edu.cnBackground: The immune environment of lung cancer is complex, and the critical immune factors that promote lung cancer progression need to be explored. Granulocytic myeloid-derived suppressor cells (G-MDSCs) are regarded as immune suppressing cells. However, they also promote tumor progression through other ways, which needs to be explored further. Therefore, we sought to study the regulatory mechanisms underlying the cancer promoting function of G-MDSCs in lung cancer.Methods: G-MDSCs were isolated from lung cancer tissues using flow cytometry. Exosomes were separated from the G-MDSCs supernatant by ultracentrifugation and verified using flow cytometry, Western blot, and transmission electron microscopy (TEM). RNA sequencing was used to identify the differential miRNAs and genes. Real-time quantitative real-time PCR (RT-qPCR) confirmed these results. The proliferation rate was assessed using the CCK-8 assay. Lentiviral vectors were used to alter the expression of the miRNAs and genes to analyze their effects on lung cancer progression.Results: G-MDSCs secreted more exosomes in the lung cancer tissues, which promoted cancer progression by accelerating proliferation. Micro RNA-143-3p (miR-143-3p) increased in G-MDSCs derived exosomes and downregulated integral membrane protein 2B (ITM2B) by targeting the 3ʹ-untranslated region (UTR) region. Overexpression of miR-143-3p enhanced proliferation by inhibiting transcription of ITM2B to activate the PI3K/Akt signaling pathway, which can be blocked by deguelin. ... |
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