American Association for Cancer Research
00085472can211473-sup-265442_2_supp_7487404_r15x95.pdf (518.64 kB)

Supplementary Information from Oncogenic circRNA C190 Promotes Non–Small Cell Lung Cancer via Modulation of the EGFR/ERK Pathway

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journal contribution
posted on 2023-03-31, 05:01 authored by Afeez Adekunle Ishola, Chian-Shiu Chien, Yi-Ping Yang, Yueh Chien, Aliaksandr A. Yarmishyn, Ping-Hsing Tsai, Jerry Chieh-Yu Chen, Po-Kuei Hsu, Yung-Hung Luo, Yuh-Min Chen, Kung-Hou Liang, Yuan-Tzu Lan, Teh-Ia Huo, Hsin-I. Ma, Ming-Teh Chen, Mong-Lien Wang, Shih-Hwa Chiou

Supplementary materials and methods, supplementary tables, and supplementary figures to support the main manuscript


Ministry of Science and Technology in Taiwan

Taipei Veterans General Hospital

Program of the Institute of Biomedical Sciences

Veterans Affairs Council



Lung cancers are the leading cause of cancer-related mortality worldwide, and the majority of lung cancers are non–small cell lung carcinoma (NSCLC). Overexpressed or activated EGFR has been associated with a poor prognosis in NSCLC. We previously identified a circular noncoding RNA, hsa_circ_0000190 (C190), as a negative prognostic biomarker of lung cancer. Here, we attempted to dissect the mechanistic function of C190 and test the potential of C190 as a therapeutic target in NSCLC. C190 was upregulated in both NSCLC clinical samples and cell lines. Activation of the EGFR pathway increased C190 expression through a MAPK/ERK-dependent mechanism. Transient and stable overexpression of C190 induced ERK1/2 phosphorylation, proliferation, and migration in vitro and xenograft tumor growth in vivo. RNA sequencing and Expression2Kinases (X2K) analysis indicated that kinases associated with cell-cycle and global translation are involved in C190-activated networks, including CDKs and p70S6K, which were further validated by immunoblotting. CRISPR/Cas13a-mediated knockdown of C190 decreased proliferation and migration of NSCLC cells in vitro and suppressed tumor growth in vivo. TargetScan and CircInteractome databases predicted that C190 targets CDKs by sponging miR-142-5p. Analysis of clinical lung cancer samples showed that C190, CDK1, and CDK6 expressions were significantly higher in advanced-stage lung cancer than in early-stage lung cancer. In summary, C190 is directly involved in EGFR–MAPK–ERK signaling and may serve as a potential therapeutic target for the treatment of NSCLC. The circRNA C190 is identified as a mediator of multiple pro-oncogenic signaling pathways in lung cancer and can be targeted to suppress tumor progression.