机构：[1]Department of Dermatology and Venereology, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.[2]Department of Dermatology, Shijiazhuang People's Hospital, Shijiazhuang, Hebei, China.[3]Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.河北医科大学第四医院[4]Key Laboratory of Tumor Prevention, Precision Diagnosis and Treatment of Hebei, Clinical Oncology Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.河北医科大学第四医院[5]Department of Pathology, Shijiazhuang People's Hospital, Shijiazhuang, Hebei, China.[6]Department of Dermatology, Shijiazhuang Gaocheng People's Hospital, Shijiazhuang, Hebei, China.
Wilms' tumour 1-associating protein (WTAP) is ubiquitously expressed in many tissues and plays an important role in physiological processes and tumour development. Here, we investigated the specific biological role and underlying mechanism of WTAP in melanoma. We determined the expression of WTAP and its correlation with clinicopathological features in paraffin-embedded tissues. We investigated the effects of WTAP on melanoma cells via a CCK-8 assay, a colony formation assay, an EdU assay, a transwell assay and subcutaneous xenograft experiments. We then applied RNA sequencing to further screen candidate targets, and NT5E was selected as the downstream gene of WTAP. Finally, a series of rescue assays together with nucleotidase assays and ELISA were adopted to confirm the function of NT5E in melanoma progression. We demonstrated that WTAP expression was downregulated in melanoma, which was associated with a poor prognosis, and that WTAP expression served as an independent predictor of melanoma survival. Functionally, WTAP hindered the proliferation, growth, migration and invasion of melanoma cells. Furthermore, NT5E was identified as the downstream effector of WTAP and was subsequently found to rescue the increased proliferation, migration and invasion of melanoma cells induced by WTAP deficiency. Moreover, knockdown of WTAP increased the expression of NT5E, MMP2 and N-cadherin, and simultaneous transfection with siNT5E reversed the increased expression of MMP2 and N-cadherin. Moreover, increased NT5E expression caused by forced WTAP inhibition in melanoma promoted the hydrolysis of AMP to produce more adenosine and further abrogated the secretion of IFN-γ by PBMCs. We found that WTAP expression is significantly downregulated and restrains the progression of melanoma via the downstream effects of NT5E on immunosuppression and molecular adhesion. This study revealed that WTAP plays a crucial inhibitory role in melanoma oncogenesis and highlighted WTAP as a potential novel diagnosis and therapeutic target for melanoma.
基金：
The present study was supported by funding from the Natural Science Foundation of Hebei Provence (No. H2022206368) and the Cultivating Programme Plan for Clinical Excellent Talent of Hebei in 2024 (No. ZF2024067).
语种：
外文
PubmedID：
中科院分区：
出版当年[2025]版：
大类|4 区医学
小类|4 区肿瘤学
最新[2025]版：
大类|4 区医学
小类|4 区肿瘤学
第一作者：
第一作者机构：[1]Department of Dermatology and Venereology, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.[2]Department of Dermatology, Shijiazhuang People's Hospital, Shijiazhuang, Hebei, China.
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Lu Huixiu,Zhang Yanli,Li Jiali,et al.WTAP is a promising diagnosis and treatment biomarker that inhibits the proliferation and invasion of melanoma cells[J].Neoplasma.2025,doi:10.4149/neo_2025_250110N12.
APA：
Lu Huixiu,Zhang Yanli,Li Jiali,Lou Dan,Li Licui...&Liu Yaling.(2025).WTAP is a promising diagnosis and treatment biomarker that inhibits the proliferation and invasion of melanoma cells.Neoplasma,,
MLA：
Lu Huixiu,et al."WTAP is a promising diagnosis and treatment biomarker that inhibits the proliferation and invasion of melanoma cells".Neoplasma .(2025)
