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

Autor: Wang LX; Department of Otorhinolaryngology, Head and Neck Surgery, the Second Affiliated Hospital of Xi'an Jiao Tong University, Xi'an, China.; Department of Otorhinolaryngology, Head and Neck Surgery, Renmin Hospital, Hubei University of Medicine, Shiyan, China., Kang ZP; Department of Andrology, Renmin Hospital, Hubei University of Medicine, Shiyan, China., Yang ZC; Department of Otorhinolaryngology, Head and Neck Surgery, General Hospital of Ningxia Medical University, Yinchuan, China., Ma RX; Department of Otorhinolaryngology, Head and Neck Surgery, General Hospital of Ningxia Medical University, Yinchuan, China., Tan Y; Department of Andrology, Renmin Hospital, Hubei University of Medicine, Shiyan, China., Peng XB; Department of Otorhinolaryngology, Head and Neck Surgery, Renmin Hospital, Hubei University of Medicine, Shiyan, China., Dai RZ; Department of Otorhinolaryngology, Head and Neck Surgery, Renmin Hospital, Hubei University of Medicine, Shiyan, China., Li J; Department of Otorhinolaryngology, Head and Neck Surgery, Renmin Hospital, Hubei University of Medicine, Shiyan, China., Yu Y; Department of Otorhinolaryngology, Head and Neck Surgery, General Hospital of Ningxia Medical University, Yinchuan, China., Xu M; Department of Otorhinolaryngology, Head and Neck Surgery, the Second Affiliated Hospital of Xi'an Jiao Tong University, Xi'an, China.
Jazyk: angličtina
Zdroj: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology [Cell Physiol Biochem] 2018; Vol. 46 (6), pp. 2232-2238. Date of Electronic Publication: 2018 May 03.
DOI: 10.1159/000489591
Abstrakt: 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.
(© 2018 The Author(s). Published by S. Karger AG, Basel.)
Databáze: MEDLINE