hsa_circ_0003222 accelerates stemness and progression of non-small cell lung cancer by sponging miR-527 |
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| Authors: | Changhui Li Jiaqi Zhang Xiaohua Yang Cheng Hu Tianqing Chu Runbo Zhong Yinchen Shen Fang Hu Feng Pan Jianlin Xu Jun Lu Xiaoxuan Zheng Hai Zhang Wei Nie Baohui Han Xueyan Zhang |
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| Institution: | 1.Department of Pulmonary, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China ;2.Shanghai TCM-Integrated Institute of Vascular Anomalies, Shanghai TCM-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200082 China ;3.Central Laboratory, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China ;4.Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203 China |
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| Abstract: | The relationship between circular RNA (circRNA) and cancer stem cells (CSCs) is uncertain. We have investigated the combined influence of CSCs, circRNA (hsa_circ_0003222), and immune checkpoint inhibitors in NSCLC progression and therapy resistance. We constructed lung CSCs (LCSCs; PC9 and A549). The effects of hsa_circ_0003222 in vitro were determined by cell counting, colony and sphere formation, and Transwell assays. A tumor xenograft model of metastasis and orthotopic model were built for in vivo analysis. We found that hsa_circ_0003222 was highly expressed in NSCLC tissues and LCSCs. Higher levels of hsa_circ_0003222 were associated with the stage, metastasis, and survival rate of patients with NSCLC. Reduced levels of hsa_circ_0003222 decreased tumor cell proliferation, migration, invasion, stemness-like properties, and chemoresistance. The silencing of hsa_circ_0003222 was found to downregulate PHF21B expression and its downstream, β-catenin by relieving the sponging effect of miR-527. Moreover, silencing hsa_circ_0003222 alleviated NSCLC resistance to anti-programmed cell death-ligand 1 (PD-L1)-based therapy in vivo. Our data demonstrate the significant role of hsa_circ_0003222 in NSCLC cell stemness-like properties. The manipulation of circRNAs in combination with anti-PD-L1 therapy may alleviate NSCLC stemness and progression.Subject terms: Cancer microenvironment, Cancer stem cells |
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