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

被引：44

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

来源：

CELL DEATH & DISEASE | 2021年 / 12卷 / 09期

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.

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页数：10

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