Xing Chengjuan, Tian Hui, Zhang Yini, Guo Kun, Tang Ying, Wang Qimin, Lv Li, Wang Lifen
Department of Pathology, The Second Affiliated Hospital of Dalian Medical University, Dalian, China.
Department of Emergency Medicine, Dalian Municipal Central Hospital Affiliated of Dalian Medical University, Dalian, China.
Front Oncol. 2020 Aug 12;10:1261. doi: 10.3389/fonc.2020.01261. eCollection 2020.
This study aimed to investigate the prognostic value and molecular mechanism of DDX39 and its effector SNAIL in melanoma. First, overexpression of DDX39 in melanoma, which was identified by database analysis, was further validated in patient tissues. Cell growth, cell cycle, cell migration, and cell invasion assays were then performed to evaluate the effects of downregulated DDX39 on the melanoma cell proliferation and aggressiveness. The same approaches were also used to reveal the cooperation of the transcription factor SNAIL with DDX39 to promote the aggressiveness of melanoma cells. We found that the expression of DDX39 was significantly upregulated in melanoma tissue compared to pigmented nevus tissue, and it was positively correlated with the clinical stage defined by the American Joint Committee on Cancer (AJCC) and the prognosis. Downregulation of DDX39 in melanoma cells was found to significantly inhibit cell proliferation, increase G2/M cell cycle arrest, enhance caspase-mediated cell apoptosis, and suppress cell invasion and migration. In addition, we demonstrated that the overexpression of SNAIL could restore the cell growth and aggressiveness impaired by DDX39 RNA interference. Immunohistochemical staining also showed a positive correlation between DDX39 overexpression and SNAIL overexpression in melanoma tissues, suggesting that SNAIL is one of the effectors activated by DDX39. In summary, the overexpression of DDX39 and SNAIL was positively related to the poor prognosis of melanoma patients and the increased aggressiveness of melanoma cells. Our study provides valuable evidence regarding the prognostic value of DDX39 and SNAIL as well as their potential as novel therapeutic targets for treating melanoma patients.
本研究旨在探讨DDX39及其效应因子SNAIL在黑色素瘤中的预后价值和分子机制。首先，通过数据库分析确定黑色素瘤中DDX39的过表达，并在患者组织中进一步验证。然后进行细胞生长、细胞周期、细胞迁移和细胞侵袭实验，以评估下调DDX39对黑色素瘤细胞增殖和侵袭性的影响。同样的方法也用于揭示转录因子SNAIL与DDX39协同促进黑色素瘤细胞侵袭性的作用。我们发现，与色素痣组织相比，黑色素瘤组织中DDX39的表达显著上调，且与美国癌症联合委员会（AJCC）定义的临床分期及预后呈正相关。在黑色素瘤细胞中下调DDX39可显著抑制细胞增殖，增加G2/M期细胞周期阻滞，增强半胱天冬酶介导的细胞凋亡，并抑制细胞侵袭和迁移。此外，我们证明SNAIL的过表达可恢复因DDX39 RNA干扰而受损的细胞生长和侵袭性。免疫组织化学染色也显示黑色素瘤组织中DDX39过表达与SNAIL过表达呈正相关，提示SNAIL是DDX39激活的效应因子之一。总之，DDX39和SNAIL的过表达与黑色素瘤患者的不良预后及黑色素瘤细胞侵袭性增加呈正相关。我们的研究为DDX39和SNAIL的预后价值及其作为治疗黑色素瘤患者新治疗靶点的潜力提供了有价值的证据。
