UTRN inhibits melanoma growth by suppressing p38 and JNK/c-Jun signaling pathways

Cancer Cell International

Huaiyuan Xu¹  Ronghua Yang²  Baiqiang Mei³  Xi Zhang⁴  Lexi Liao⁵  Jiehua Li⁶  Sitong Zhou⁶  Xiaobing Pi⁶  Shijian Xiang⁷  Wen Ouyang⁸ 

[1] Department of Bone and Soft Tissue Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China;Department of Burn Surgery and Skin Regeneration, The First People’s Hospital of Foshan, Foshan, Guangdong, China;Department of Cardiovascular Disease, The First People’s Hospital of Foshan, Foshan, Guangdong, China;Department of Dermatology, Binzhou Medical University Hospital, Binzhou, Shandong, China;Department of Dermatology, Cosmetology and Venereology, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, China;Department of Dermatology, The First People’s Hospital of Foshan, 81 Lingnan Avenue North, 528000, Foshan, Guangdong, China;Department of Pharmacy, Seventh Affiliated Hospital of Sun Yat-Sen University, 518107, Shenzhen, China;The Second Clinical Medical College, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China;

关键词: UTRN;    Survival analysis;    Melanoma;    TCGA;    GSEA;   

DOI  :  10.1186/s12935-021-01768-4

来源: Springer

【 摘 要 】

BackgroundUtrophin (UTRN), as a tumor suppressor gene, is involved in various cancer progression. The function of UTRN in the melanoma process and the related molecular mechanisms are still unclear. Herein, we studied the function of UTRN in melanoma growth and the relevant molecular mechanisms.MethodsUsing the GEO database and UCSC Xena project, we compared the expression of UTRN in non-cancerous and melanoma tissues. Immunohistochemistry (IHC) staining, qRT-PCR and Western Blot (WB) were performed to evaluate UTRN expression in clinical samples. A total of 447 cases with UTRN expression data, patient characteristics and survival data were extracted from TCGA database and analyzed. After stable transduction and single cell cloning, the proliferation ability of A375 human melanoma cells was analyzed by Cell Counting Kit‑8 (CCK) and 5‑ethynyl‑2′‑deoxyuridine (EdU) incorporation assays. GSEA was performed to predict the mechanism by which UTRN regulated melanoma growth. Then WB analysis was used to assess the protein expression levels of pathway signaling in overexpression (EXP) melanoma cells. Epac activator 8-pCPT-2′-O-Me-cAMP was then used to evaluate the proliferation ability by activation of p38 and JNK/c-Jun signaling pathways.ResultsData from GEO and UCSC Xena project indicated that UTRN expression was decreased in melanoma. Experiment on clinical samples further confirmed our finding. TCGA results showed that a reduced expression of UTRN in 447 melanoma samples was associated with advanced clinical characteristics (T stage, Clark level, ulceration), shorter survival time and poorer prognosis. In addition, up-regulated UTRN expression inhibited melanoma cell proliferation when compared to control group. MAPK signaling pathway was presented in both KEGG and BioCarta databases by using GSEA tool. WB results confirmed the down-regulated expression of p38, JNK1 and c-Jun in EXP group when compared to control group. Epac activator 8-pCPT-2′-O-Me-cAMP treatment could partially rescue proliferation of tumor cells.ConclusionWe have demonstrated that reduced UTRN predicted poorer prognosis and UTRN inhibited melanoma growth via p38 and JNK1/c-Jun pathways. Therefore, UTRN could serve as a tumor suppressor and novel prognostic biomarker for melanoma patients.

【 授权许可】

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