circ_0004140 promotes LUAD tumor progression and immune resistance through circ_0004140/miR-1184/CCL22 axis

• Main Authors: Liang, X. (Author), Liu, Y. (Author), Lu, P. (Author), Luo, J. (Author), Ma, Y. (Author), Xiang, L. (Author), Xiong, L. (Author), Xu, H. (Author), Yin, Z. (Author), Zhang, H. (Author), Zhang, W. (Author), Zhang, X. (Author)
• Format: Article
• Language: English
• Published: Springer Nature 2022
• Online Access: View Fulltext in Publisher
• ISBN: 20587716 (ISSN)
• DOI: 10.1038/s41420-022-00983-w

Lung adenocarcinoma (LUAD) is a highly prevalent cancer with high mortality. Immune resistance and tumor metastasis are the pivotal factors for the promotion of LUAD. CircRNAs have been revealed a crucial pre-clinical diagnostic and therapeutic potentials in LUAD. Herein, we identify a novel circRNA (circ_0004140), derived from the oncogene YAP1, which is up-regulated in LUAD. The high expression of circ_0004140 is correlated with poor prognosis and CTL cells dysfunction in LUAD patients. Knockdown of circ_0004140 regulated LUAD cells proliferation, migration, and apoptosis. Mechanistically, circ_0004140 served as a sponge of miR-1184 targeting C-C motif chemokine ligand 22(CCL22). Overexpression of CCL22 reversed the inhibitory effect induced by si-circ_0004140 on cells proliferation and migration. Moreover, we also revealed that elevated circ_ooo4140 was related to cytotoxic lymphocyte exhaustion, and a combination therapy of C-021 (CCL22/CCR4 axis inhibitor) and anti-PD-1 attenuated LUAD promotion and immune resistance. In conclusion, circ_0004140 may drive resistance to anti-PD-1 immunotherapy, providing a novel potential therapeutic target for LUAD treatment. © 2022, The Author(s).