NDLI: The oncogenic role of HIF-1α/miR-182-5p/ZFP36L1 signaling pathway in nasopharyngeal carcinoma

Content Provider	Springer Nature : BioMed Central
Author	Wang, Gang Zhou, Fangzheng Ou, Tong Sun, Haiyan Shan, Zhirui Lu, Yingshen Chen, Gui Yuan, Simin Zhang, Xiaowen Wu, Song
Abstract	Background Accumulating evidence indicates that dysregulation of miR-182-5p can serve as diagnostic and prognostic biomarkers for some cancers, whereas the role of miR-182-5p has not been explored in nasopharyngeal carcinoma (NPC). Our study aims to elucidate the biological function of miR-182-5p in NPC and the potential molecular mechanism involved. Methods Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to determine miR-182-5p expression in NPC primary tissues and cell lines. Immunohistochemistry (IHC) for ZFP36L1 was conducted in NPC samples. Western blot was used to evaluate protein expression in cell lines. A series of functional assays were carried out to evaluate the roles of miR-182-5p and ZFP36L1 in tumor development and progression of NPC. Bioinformatics tools and luciferase reporter assays were utilized to identify the potential mechanisms of action. Moreover, rescue experiments were applied to explore whether ZFP36L1 mediated the effects of miR-182-5p in NPC. Results Up-regulation of miR-182-5p was significantly associated with tumor development and poor prognosis in patients with NPC. Functional study demonstrated that miR-182-5p overexpression enhanced, whereas suppression of miR-182-5p impeded NPC cell proliferation, migration, tumorigenesis and metastasis. Mechanistically, miR-182-5p interacted with ZFP36L1 at two sites in its 3′ un-translated region (UTR) and repressed ZFP36L1 expression in NPC. Consistently, an inverse correlation was observed between the expression levels of miR-182-5p and ZFP36L1 using clinical NPC tissues, and down-regulation of ZFP36L1 in NPC predicts poor survival. Furthermore, overexpression of miR-182-5p in NPC was partly attributable to the transcriptional activation effect induced by hypoxia-inducible factor 1α (HIF-1α). Conclusions Our data suggests that miR-182-5p facilitates cell proliferation and migration in NPC through its ability to down-regulate ZFP36L1 expression, and that the HIF-1α/miR-182-5p/ZFP36L1 axis may serve as a novel therapeutic target in the management of NPC.
Related Links	https://cancerci.biomedcentral.com/counter/pdf/10.1186/s12935-021-02177-3.pdf
Ending Page	12
Page Count	12
Starting Page	1
File Format	HTM / HTML
ISSN	14752867
DOI	10.1186/s12935-021-02177-3
Journal	Cancer Cell International
Issue Number	1
Volume Number	21
Language	English
Publisher	BioMed Central
Publisher Date	2021-08-31
Access Restriction	Open
Subject Keyword	Cancer Research Cell Biology miR-182-5p ZFP36L1 HIF-1α Tumorigenesis Metastasis Nasopharyngeal carcinoma
Content Type	Text
Resource Type	Article
Subject	Cancer Research Genetics Oncology
Journal Impact Factor	5.3/2023
5-Year Journal Impact Factor	5/2023

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