Affiliations: Department of Otolaryngology, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang, Henan, China
Correspondence:
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Corresponding author: Yong Zhang, Department of Otolaryngology, Luoyang Central Hospital Affiliated to Zhengzhou University, No. 288 Zhongzhou Middle Road, Luoyang, Henan, 471000, China. E-mail: [email protected].
Abstract: BACKGROUND: Foxhead box D1 (FOXD1) is validated to be over-expressed in a variety of human malignancies and promotes cancer progression. Nevertheless, the role of FOXD1 and the associated mechanism in nasopharyngeal carcinoma (NPC) remain largely unknown. METHODS: A total of seventy-five cases of NPC tissue samples were collected. FOXD1 expression in NPC tissues and cells (SUNE1, CNE1, CNE2, and HONE1) was detected using immunohistochemistry and Western blot, respectively. The relationship between FOXD1 expression and clinicopathological parameters of NPC patients was analyzed. FOXD1 mRNA and miR-186 expression in NPC tissues and cells was detected using quantitative polymerase chain reaction (qPCR). The cell viability of NPC cells was detected using CCK-8 assay. Colony survival of NPC cells exposed to different doses of radiation was detected using colony formation assay. Transwell assay was used to evaluate the migration and invasion of NPC cells. The dual-luciferase reporter gene assay was employed to verify the targeting relationship between miR-186 and FOXD1. RESULTS: FOXD1 was over-expressed in NPC tissues (average fold change on mRNA level = 4.72), and its high expression was correlated to NPC positive lymph node metastasis and tissue differentiation. The over-expression of FOXD1 promoted the proliferation, migration, invasion and radio-resistance of NPC cells. On the contrary, the knock-down of FOXD1 inhibited the malignant phenotypes of the above cells. It was verified that FOXD1 was one of the downstream targets of miR-186 and was negatively regulated by it. CONCLUSION: FOXD1, which is negatively regulated by miR-186, acts as a novel oncogene in NPC and serves as potential biomarker and therapeutic target for NPC. The research will provide great theoretical basis for further clinical diagnosis and therapy.
