hsa_circ_0003222 accelerates stemness and progression of non-small cell lung cancer by sponging miR-527

被引:45
作者
Li, Changhui [1 ]
Zhang, Jiaqi [2 ]
Yang, Xiaohua [3 ]
Hu, Cheng [4 ]
Chu, Tianqing [1 ]
Zhong, Runbo [1 ]
Shen, Yinchen [1 ]
Hu, Fang [1 ]
Pan, Feng [1 ]
Xu, Jianlin [1 ]
Lu, Jun [1 ]
Zheng, Xiaoxuan [1 ]
Zhang, Hai [1 ]
Nie, Wei [1 ]
Han, Baohui [1 ]
Zhang, Xueyan [1 ]
机构
[1] Shanghai Jiao Tong Univ, Shanghai Chest Hosp, Dept Pulm, Shanghai, Peoples R China
[2] Shanghai Univ Tradit Chinese Med, Shanghai TCM Integrated Inst Vasc Anomalies, Shanghai TCM Integrated Hosp, Shanghai 200082, Peoples R China
[3] Shanghai Jiao Tong Univ, Shanghai Chest Hosp, Cent Lab, Shanghai, Peoples R China
[4] Shanghai Univ Tradit Chinese Med, Expt Ctr Sci & Technol, Shanghai 201203, Peoples R China
关键词
CIRCULAR RNA; PROLIFERATION; EPIDEMIOLOGY; EXPRESSION; MIGRATION; INVASION; NSCLC;
D O I
10.1038/s41419-021-04095-8
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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, beta-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.
引用
收藏
页数:10
相关论文
共 40 条
[1]   Lung Cancer 2020 Epidemiology, Etiology, and Prevention [J].
Bade, Brett C. ;
Dela Cruz, Charles S. .
CLINICS IN CHEST MEDICINE, 2020, 41 (01) :1-+
[2]   Recent Advances in Cancer Stem Cell-Targeted Immunotherapy [J].
Badrinath, Narayanasamy ;
Yoo, So Young .
CANCERS, 2019, 11 (03)
[3]   Global Epidemiology of Lung Cancer [J].
Barta, Julie A. ;
Powell, Charles A. ;
Wisnivesky, Juan P. .
ANNALS OF GLOBAL HEALTH, 2019, 85 (01)
[4]   PHF21B as a candidate tumor suppressor gene in head and neck squamous cell carcinomas [J].
Bertonha, Fernanda Bernardi ;
Barros Filho, Mateus de Camargo ;
Kuasne, Hellen ;
dos Reis, Patricia Pintor ;
Prando, Erika da Costa ;
Augusto Moyano Munoz, Juan Jose ;
Roffe, Martin ;
Maroso Hajj, Glaucia Noeli ;
Kowalski, Luiz Paulo ;
Rainho, Claudia Aparecida ;
Rogatto, Silvia Regina .
MOLECULAR ONCOLOGY, 2015, 9 (02) :450-462
[5]   A novel circular RNA, hsa_circ_0043278, acts as a potential biomarker and promotes non-small cell lung cancer cell proliferation and migration by regulating miR-520f [J].
Cui, Jinggang ;
Li, Wei ;
Liu, Guohua ;
Chen, Xiaojun ;
Gao, Xiaolai ;
Lu, Huiling ;
Lin, Dang .
ARTIFICIAL CELLS NANOMEDICINE AND BIOTECHNOLOGY, 2019, 47 (01) :810-821
[6]   Non-Small Cell Lung Cancer: Epidemiology, Screening, Diagnosis, and Treatment [J].
Duma, Narjust ;
Santana-Davila, Rafael ;
Molina, Julian R. .
MAYO CLINIC PROCEEDINGS, 2019, 94 (08) :1623-1640
[7]   Circular RNA hsa_circ_0014130 Inhibits Apoptosis in Non-Small Cell Lung Cancer by Sponging miR-136-5p and Upregulating BCL2 [J].
Geng, Ying ;
Bao, Yongxia ;
Zhang, Wei ;
Deng, Lili ;
Su, Dongju ;
Zheng, Hongyan .
MOLECULAR CANCER RESEARCH, 2020, 18 (05) :748-756
[8]   Maintenance Chemotherapy for Advanced Non-Small-Cell Lung Cancer: New Life for an Old Idea [J].
Gerber, David E. ;
Schiller, Joan H. .
JOURNAL OF CLINICAL ONCOLOGY, 2013, 31 (08) :1009-1020
[9]   Toxicity management with combination chemotherapy and programmed death 1/programmed death ligand 1 inhibitor therapy in advanced lung cancer [J].
Hoffner, Brianna ;
Leighl, Natasha B. ;
Davies, Marianne .
CANCER TREATMENT REVIEWS, 2020, 85
[10]   MicroRNA-527 inhibits TGF-β/SMAD induced epithelial-mesenchymal transition via downregulating SULF2 expression in non-small-cell lung cancer [J].
Huo, Wei ;
Zhu, Xiao-Min ;
Pan, Xin-Yan ;
Du, Min ;
Sun, Zhuo ;
Li, Zhi-Min .
MATHEMATICAL BIOSCIENCES AND ENGINEERING, 2019, 16 (05) :4607-4621