MicroRNA-135a Inhibits Nasopharyngeal Carcinoma Cell Proliferation Through Targeting Interleukin-17

• Published in: Cellular physiology and biochemistry Vol. 46; no. 6; pp. 2232 - 2238
• Main Authors: Wang, Li-Xin, Kang, Zhao-Peng, Yang, Zhi-Chao, Ma, Rui-Xia, Tan, Yan, Peng, Xian-Bing, Dai, Run-Zhi, Li, Jin, Yu, Yang, Xu, Min
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01.01.2018; Cell Physiol Biochem Press GmbH & Co KG
• Subjects: Angiogenesis; Biochemistry; Breast cancer; Carcinoma - blood; Carcinoma - genetics; Cell growth; Cell Proliferation; Cytokines; Cytotoxicity; Down-Regulation; Female; Gene expression; Gene Expression Regulation, Neoplastic; Humans; IL-17; Interleukin-17 - blood; Interleukin-17 - genetics; Lung cancer; Male; MicroRNAs; MicroRNAs - genetics; MiR-135a; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms - blood; Nasopharyngeal Neoplasms - genetics; Original Paper; Pathogenesis; Physiology; Plasma; Proinflammatory cytokines; Throat cancer; Tumor Cells, Cultured; Tumors; China; Nasopharyngeal carcinoma; MiR-135a; Proinflammatory cytokines; IL-17
• ISSN: 1015-8987; 1421-9778; 1421-9778
• DOI: 10.1159/000489591

Background/Aims: The objective of this study was to investigate the potential role of IL-17 in the development of nasopharyngeal carcinoma (NPC) and to screen microRNAs (miRNAs) that potentially target IL-17 in NPC cells. Methods: Blood was collected from NPC patients and normal subjects, and plasma IL-17 concentration was quantified by enzyme-linked immunosorbent assay. An immortalized normal human nasopharyngeal epithelial cell line, NP69, was treated with or without human IL-17 (15 ng/mL) for various times, and expression of IL-1ß, IL-6, IL-12, and TNF-α mRNA was assessed by real-time reverse transcription PCR. The candidate miRNAs that potentially target IL-17 were predicted by a bioinformatics strategy. The selected miR-135a mimic was transfected into primary NPC cells, and cell proliferation was assessed by MTT assay. Results: The concentration of plasma IL-17 was significantly higher in the NPC patients (92.5 ± 7.3 pg/mL) than in the control subjects (56.8 ± 2.9 pg/mL). In response to IL-17 treatment, the mRNA expression of IL-1ß and IL-6 was significantly upregulated and reached a peak at 12 h, followed by a slight decrease at 24 h, while the mRNA expression of IL-12 and TNF-α was significantly upregulated at 12 h and remained high even at 48 h after exposure to IL-17. Moreover, miR-135a specifically targets IL-17 and was dramatically downregulated in NPC cells compared with NP69 cells. Transfection of exogenous miR-135a mimic resulted in significant suppression of IL-17 secretion and subsequent inhibition of NPC cell proliferation. Conclusions: Blood IL-17 was significantly higher in NPC patients compared with normal subjects. Expression of miR-135a in the cancer cells isolated from nasopharyngeal tumors was significantly lower than that in NP69 cells, and suppression of IL-17 by miR-135a mimic resulted in significant inhibition of NPC cell proliferation. These findings suggested that downregulation of miR-135a may contribute to the development of NPC via the mechanism of IL-17 stimulation of proinflammatory cytokine expression.