Oncotarget

Research Papers:

CCAR2 negatively regulates IL-8 production in cervical cancer cells

Wootae Kim, Jaehyuk Pyo, Byeong-Joo Noh, Joo-Won Jeong, Juhie Lee and Ja-Eun Kim _

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Oncotarget. 2018; 9:1143-1155. https://doi.org/10.18632/oncotarget.23199

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Abstract

Wootae Kim1, Jaehyuk Pyo1, Byeong-Joo Noh2, Joo-Won Jeong1,3, Juhie Lee2 and Ja-Eun Kim1,4

1Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea

2Department of Pathology, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea

3Department of Anatomy and Neurobiology, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea

4Department of Pharmacology, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea

Correspondence to:

Ja-Eun Kim, email: [email protected]

Keywords: CCAR2; IL-8; oxidative stress; cervical cancer

Received: September 06, 2017     Accepted: October 27, 2017     Published: December 13, 2017

ABSTRACT

Cell cycle and apoptosis regulator 2 (CCAR2) is a multifaceted protein that controls diverse cellular functions; however, its function in cancer is unclear. To better understand its potential role in cancer, we examined gene expression patterns regulated by CCAR2 in cervical cancer cells. Cytokine and chemokine production by CCAR2-deficient cells increased under oxidative conditions. In particular, H2O2-treated CCAR2-depleted cells showed a significant increase in interleukin-8 (IL-8) production, indicating a negative regulation of IL-8 by CCAR2. Upregulation of IL-8 expression in CCAR2-deficient cells occurred via activation of transcription factor AP-1. The negative correlation between CCAR2 and IL-8 expression was confirmed by examining mRNA and protein levels in tissues from cervical cancer patients. Furthermore, CCAR2-regulated IL-8 expression is associated with a shorter survival of cervical cancer patients. Overall, the data suggest that CCAR2 plays a critical role in controlling both the cancer secretome and cancer progression.


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