Yaqi Wang, Hui Su, Xiaopeng Wang, Chen Tu, Tong Xiao, Bincheng Ren, Shuang Wang
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引用次数: 0
Abstract
Background: The forkhead box (FOX) family member FOXN3 has been reported to inhibit transcriptional activity associated with regulating tumor development. However, the role of FOXN3 in the pathogenesis of melanoma is not well understood.
Objective: To investigate the biological functions of FOXN3 in drug resistance of melanoma.
Materials and methods: The expression of FOXN3 in melanoma was investigated using Gene Expression profiling interactive analysis (GEPIA) and Linkedomics databases. Melanoma cell proliferation, invasion, and migration were assessed using the colony formation assay, the scratch wound healing test, the Transwell invasion assay, and the nude mice xenograft to determine the effects of FOXN3 over-expression and depletion. The functional role of the transcriptional regulator in melanoma cells was tested through chromatin immunoprecipitation, immunofluorescence.
Results: FOXN3 was downregulated in melanoma. Over-expression of FOXN3 inhibited the proliferation and motility of melanoma cells, whereas FOXN3 knockdown significantly enhanced the proliferation and motility of melanoma cells. Overexpression of FOXN3 reduced autophagic activity in melanoma cells. Enhanced autophagic activity in drug-resistant melanoma cell lines is related to drug-sensitive cells, and significant differences in FOXN3 localization were observed when comparing melanoma cells that were sensitive and resistant to Vemurafenib. Additionally, FOXN3 has been identified as binding to the promoter region of the cancer antigen Fibrous Sheath Interacting Protein 1 (FSIP1), thereby regulating the expression of this gene.
Conclusion: FOXN3 functions as an important regulator of the development and progression of Vemurafenib-resistant melanoma cells, partly owing to its binding to the FISP1. As such, FOXN3 may represent a relevant target for therapeutic interventions in patients suffering from drug-resistant melanoma.
期刊介绍：
Clinical, Cosmetic and Investigational Dermatology is an international, peer-reviewed, open access journal that focuses on the latest clinical and experimental research in all aspects of skin disease and cosmetic interventions. Normal and pathological processes in skin development and aging, their modification and treatment, as well as basic research into histology of dermal and dermal structures that provide clinical insights and potential treatment options are key topics for the journal.
Patient satisfaction, preference, quality of life, compliance, persistence and their role in developing new management options to optimize outcomes for target conditions constitute major areas of interest.
The journal is characterized by the rapid reporting of clinical studies, reviews and original research in skin research and skin care.
All areas of dermatology will be covered; contributions will be welcomed from all clinicians and basic science researchers globally.
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