LncRNA HOTAIR contributes to the tumorigenesis of nasopharyngeal carcinoma via up-regulating FASN

D.-D. Ma, L.-L. Yuan, L.-Q. Lin

Department of Otorhinolaryngology, Affiliated Hospital of Jining Medical College, Jining, China. ylljnmc@163.com

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• Oncology

OBJECTIVE: The therapeutic options for nasopharyngeal carcinoma (NPC) treatment have been restricted mainly to radiotherapy or chemotherapy, and the clinical treatment effect remains unsatisfactory. The primary purpose of this study was to investigate the molecular mechanisms of NPC and to find effective novel therapeutic targets for NPC.

PATIENTS AND METHODS: In order to analyze the expression level of lncRNA HOTAIR and FASN in human NPC clinical tissues or NPC cells, total RNA was extracted with TRIzol and the relative mRNA expression levels were detected by quantitative Real-time PCR. The endogenous expression of HOTAIR was modulated using lentivirus vectors transfection. The protein levels of Fatty acid synthase (FASN), p21 and MMP-9 in NPC cells were determined by Western blot when HOTAIR was knockdown. A free Fatty acid quantitation assay was performed to detect the intracellular free Fatty acid in NPC cells. The CCK-8 and colony formation assays were performed for cell viability and proliferation determination. The cell cycle of NPC cells was also determined by flow cytometric analysis. A matrigel invasion assay was performed to analyze the invasive ability of NPC cells.

RESULTS: In this study, we observed a significant upregulation of lncRNA HOTAIR in NPC cells and clinical NPC specimens. The expression of Fatty acid synthase (FASN) was positively correlated to HOTAIR in NPC specimens. Knockdown of HOTAIR led to downregulation of FASN in NPC cells, thus suppressing cell proliferation and invasion. Additionally, de novo synthesis of cellular free fatty acid in NPC cells was inhibited when HOTAIR was knockdown. Furthermore, the protein levels of MMP-9 and p21 were downregulated when HOTAIR was knockdown.

CONCLUSIONS: We suggest that HOTAIR is important in the progression and recurrence of NPC, perhaps through upregulating FASN. Targeting HOTAIR may be an effective therapeutic strategy for NPC.

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