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

Authors
  • Li, Changhui1
  • Zhang, Jiaqi2
  • Yang, Xiaohua1
  • Hu, Cheng3
  • Chu, Tianqing1
  • Zhong, Runbo1
  • Shen, Yinchen1
  • Hu, Fang1
  • Pan, Feng1
  • Xu, Jianlin1
  • Lu, Jun1
  • Zheng, Xiaoxuan1
  • Zhang, Hai1
  • Nie, Wei1
  • Han, Baohui1
  • Zhang, Xueyan1
  • 1 Shanghai Jiao Tong University, Shanghai, China , Shanghai (China)
  • 2 Shanghai University of Traditional Chinese Medicine, Shanghai, 200082, China , Shanghai (China)
  • 3 Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China , Shanghai (China)
Type
Published Article
Journal
Cell Death and Disease
Publisher
Springer Nature
Publication Date
Aug 25, 2021
Volume
12
Issue
9
Identifiers
DOI: 10.1038/s41419-021-04095-8
Source
Springer Nature
Disciplines
  • article
License
Green

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.

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