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Oncogenic circRNA C190 Promotes Non-Small Cell Lung Cancer via Modulation of the EGFR/ERK Pathway

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- Ma, Ming-Teh Chen, Mong-Lien Wang, Shih-Hwa Chiou

CANCER RESEARCH(2022)

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摘要
Lung cancers are the leading cause of cancer-related mortality worldwide, and the majority of lung cancers are non-small cell lung 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,
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关键词
non–small cell lung cancer,lung cancer,egfr/erk
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