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Oncogenic circRNA C190 Promotes Non-Small Cell Lung Cancer via Modulation of the EGFR/ERK Pathway.
Ishola, Afeez Adekunle; Chien, Chian-Shiu; Yang, Yi-Ping; Chien, Yueh; Yarmishyn, Aliaksandr A; Tsai, Ping-Hsing; Chen, Jerry Chieh-Yu; Hsu, Po-Kuei; Luo, Yung-Hung; Chen, Yuh-Min; Liang, Kung-Hou; Lan, Yuan-Tzu; Huo, Teh-Ia; Ma, Hsin-I; Chen, Ming-Teh; Wang, Mong-Lien; Chiou, Shih-Hwa.
Afiliação
  • Ishola AA; Taiwan International Graduate Program in Molecular Medicine, National Yang Ming Chiao Tung University and Academia Sinica, Taipei, Taiwan.
  • Chien CS; Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.
  • Yang YP; Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.
  • Chien Y; Institute of Pharmacology, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
  • Yarmishyn AA; School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
  • Tsai PH; Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.
  • Chen JC; School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
  • Hsu PK; Institute of Food Safety and Health Risk Assessment, School of Pharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan.
  • Luo YH; Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.
  • Chen YM; Institute of Pharmacology, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
  • Liang KH; School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
  • Lan YT; Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.
  • Huo TI; Institute of Pharmacology, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
  • Ma HI; Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.
  • Chen MT; Institute of Pharmacology, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
  • Wang ML; School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
  • Chiou SH; Taiwan International Graduate Program in Molecular Medicine, National Yang Ming Chiao Tung University and Academia Sinica, Taipei, Taiwan.
Cancer Res ; 82(1): 75-89, 2022 01 01.
Article em En | MEDLINE | ID: mdl-34753774
ABSTRACT
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.

SIGNIFICANCE:

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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Oncogenes / Carcinoma Pulmonar de Células não Pequenas / RNA Circular / Neoplasias Pulmonares Tipo de estudo: Prognostic_studies Limite: Animals / Humans / Male Idioma: En Revista: Cancer Res Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Taiwan

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Oncogenes / Carcinoma Pulmonar de Células não Pequenas / RNA Circular / Neoplasias Pulmonares Tipo de estudo: Prognostic_studies Limite: Animals / Humans / Male Idioma: En Revista: Cancer Res Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Taiwan