2020 Journal of B.U.ON. : official…

Downregulation of miR-204 facilitates the progression of nasopharyngeal carcinoma by targeting CXCR4 through NF-kappaB signaling pathway.

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Journal of B.U.ON. : official journal of the Balkan Union of Oncology Vol. 25 (2) : 1098-1104 • Mar 2020

PURPOSE: Nasopharyngeal carcinoma (NPC) is a highly invasive and metastatic cancer. The alterations of miRNA deregulation and pathway have been reported to be implicated in NPC progression. Here, we aimed to explore miR-204 role and mechanism in NPC development. METHODS: We examined the expression level of miR-204 in NPC tissues and NPC cells (HONE-1, 6-10B, HNE1) using reverse-transcription quantitative PCR (RT-qPCR) analysis. MTT, and transwell assays were used to analyze the effects of miR-204 on the proliferation, invasion and migration of NPC cells. Luciferase reporter gene assays were used to confirm the target gene of miR-204 in NPC cells. RESULTS: The results showed that miR-204 was downregulated, while CXCR4 was upregulated in NPC samples and cells with important functional consequences. Also, miR-204 expression was inversely correlated to CXCR4 expression and it was also associated with the clinicopathologic features. Ectopic expression of miR-204 was significantly suppressed, whereas downregulation of miR-204 facilitated the capacities of NPC cells proliferation, invasion and migration. Besides, it was also found that miR-204 mimic strongly decreased CXCR4 expression and miR-204 inhibitor increased CXCR4 expression. Furthermore, luciferase assay results demonstrated that CXCR4 was the direct target of miR-204. Conversely to miR-204 effect, knockdown of CXCR4 showed an inhibitory effect on NPC cell progression. Mechanistic investigations revealed that miR-204 regulated NF-kappaB signaling via CXCR4. CONCLUSION: Taken together, our findings suggested that miR-204 regulated NPC progression by targeting CXCR4 through NF-kappaB signaling pathway.

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