文章：

干扰核蛋白Laminb1诱导DNA损伤并降低黑色素瘤细胞体外对维莫非尼的耐药性

Interfering Nuclear Protein Laminb1 Induces DNA Damage and Reduces Vemurafenib Resistance in Melanoma Cells In Vitro

原文发布日期：4 December 2024

DOI: 10.3390/cancers16234060

类型: Article

开放获取: 是

英文摘要：

Background/Objectives: Drug resistance poses a substantial clinical challenge in melanoma treatment, yet the underlying mechanism remains elusive. Here, we report the novel role of laminB1, a nuclear structure protein, in regulating the response of BRAF-mutated melanoma cells to vemurafenib. Results: Our analysis of clinical samples and existing databases highlights the tight correlation between the laminB1 expression level and melanoma progression and prognosis. Notably, we observe that laminB1 expression is upregulated when BRAF-mutated melanoma cells develop resistance to vemurafenib. The knockdown of laminB1 substantially increases the sensitivity of melanoma cells to vemurafenib. Furthermore, we found laminB1 suppression increases cell apoptosis via the escalation of DNA damage in a vemurafenib-dose-dependent manner. Conversely, protective cell autophagy is negatively regulated by laminB1 suppression. Interestingly, this distinct regulation pattern of apoptosis and autophagy by laminB1 cooperatively promotes the response of BRAF-mutated melanoma cells to vemurafenib. Conclusions: Our findings unveil the potential of laminB1 as both a diagnosis marker and a therapeutic target of melanoma.

摘要翻译： 

背景/目的：耐药性是黑色素瘤治疗中的重大临床挑战，但其潜在机制尚不明确。本研究揭示了核结构蛋白laminB1在调控BRAF突变黑色素瘤细胞对维莫非尼反应中的新功能。结果：通过对临床样本及现有数据库的分析，我们发现laminB1表达水平与黑色素瘤进展及预后密切相关。值得注意的是，当BRAF突变黑色素瘤细胞对维莫非尼产生耐药性时，laminB1表达呈现上调趋势。敲低laminB1能显著增强黑色素瘤细胞对维莫非尼的敏感性。进一步研究发现，抑制laminB1可通过增加DNA损伤以维莫非尼剂量依赖的方式促进细胞凋亡。相反，保护性细胞自噬则受到laminB1抑制的负向调控。值得注意的是，laminB1对细胞凋亡和自噬的这种差异化调控模式，共同促进了BRAF突变黑色素瘤细胞对维莫非尼的治疗反应。结论：我们的研究揭示了laminB1作为黑色素瘤诊断标志物和治疗靶点的双重潜力。

原文链接：

Interfering Nuclear Protein Laminb1 Induces DNA Damage and Reduces Vemurafenib Resistance in Melanoma Cells In Vitro