MiR-506 suppresses proliferation,migration,and invasion of melanoma cells by modula-ting EMT and DNA damage homologous recombination repair pathway
LI Ting
XIANG Lijie
FU Laihua
HAO Mengze
LIU Xinyue
YANG Jilong
Abstract：Objective To investigate the biological function of miR-506 in malignant melano-ma and its regulatory mechanism on mesenchymal epithelial transition(MET)and DNA damage homologous recombination repair pathway.Methods The expression of miR-506 in 48 cases of fresh malignant melanoma tissues was detected by qRT-PCR.The expression of MET and DNA damage-related proteins in the tissues of 147 patients with malignant melanoma were detected by IHC.The human malignant melanoma cell lines A375 and A875 were used for assessing cell func-tion.Following overexpression or inhibition of miR-506,cell function assays such as MTT and Transwell chamber experiments were conducted to verify its effects on the proliferation,migration,and invasion of malignant melanoma cells.Western blot analysis was used to further examine the impact of miR-506 on the expression of MET-related proteins and homologous recombination path-ways of DNA damage.Survival analysis using Kaplan Meier method.Results The expression levels of miR-506 were low in metastatic lesions and high in primary lesions.Its high expression was associated with longer overall survival (OS) (P=0.002),disease-free survival(DFS)(P＜0.001)and progression-free survival(PFS)(P=0.041).High expression levels of mesenchy-mal marker N-cadherin indicated poorer overall survival(P=0.026),while high expression lev-els of epithelial marker E-cadherin indicated better overall survival(P=0.006).High expression levels of DNA damage homologous recombination related proteins RAD51 and ATM were associat-ed with poor OS(RAD51:P=0.014,ATM:P=0.002),while high expression of RAD52 was associated with good OS(P=0.006).Spearman correlation analysis showed that miR-506 was negatively correlated with the expression of Vimentin and Slug(r=-0.38,P=0.008;r=-0.36,P=0.012),and also negatively correlated with RAD51(r=-0.47,P=0.001).Functional cell assays showed that overexpression of miR-506 inhibited the proliferation,migra-tion,and invasion of malignant melanoma cells.Overexpression of miR-506 decreased the expres-sion of N-cadherin,Vimentin,Slug,and RAD51.Conclusions MiR-506,MET-associated pro-teins,and DNA damage homologous recombination-associated proteins are associated with the prognosis of patients with malignant melanoma.As a tumor suppressor gene,miR-506 may inhibit the proliferation,migration,and invasion of melanoma cells by regulating MET-related proteins and the homologous recombination repair pathway.
Keywords：malignant melanomamiR-506mesenchymal epithelial transformationDNA damage homologous recombination repair
Publication Date：2025-07-28
Online Publishing Date：2025-08-20(First online date of this platform, not the publication date of the document)
Pages：13( 463-475 )