Malignant melanoma (MM) is a neoplasm that develops from human melanocytes. It was reported that eukaryotic translation initiation factor 3 subunit B (EIF3B) is associated with multiple types of cancers, but its role in MM has not been reported. In the present study, we found that EIF3B was abundantly expressed in MM and was strongly related to lymphatic metastasis and pathological stage of MM patients. In addition, EIF3B depletion could block the progression of MM in vitro and in vivo. In contrast, EIF3B overexpression increased cell proliferation and migration in melanoma cells. More importantly, we identified that EIF3B's driver role in MM was mediated by PTGS2. In detail, we found that EIF3B stabilized PTGS2 expression by inhibiting PTGS2 ubiquitination, which is mediated by the E3 ligase MDM2. Moreover, like EIF3B, silencing PTGS2 could suppress MM development, and more interestingly, it could reverse the situation caused by overexpression of EIF3B in vitro and in vivo. Furthermore, the proliferation and migration inhibited by silencing of EIF3B were also partially recovered by overexpression of PTGS2. Overall, our findings revealed the potential of EIF3B as a therapeutic target for MM. Identification of EIF3B's function in MM may pave the way for future development of more specific and more effective targeted therapy strategies against MM.

中文翻译：

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EIF3B通过对抗MDM2介导的泛素化稳定PTGS2表达促进恶性黑色素瘤的发生发展

恶性黑色素瘤 (MM) 是一种从人类黑色素细胞发展而来的肿瘤。据报道，真核翻译起始因子 3 亚基 B (EIF3B) 与多种类型的癌症有关，但其在 MM 中的作用尚未见报道。在本研究中，我们发现 EIF3B 在 MM 中大量表达，并且与 MM 患者的淋巴结转移和病理分期密切相关。此外，EIF3B 耗竭可以在体外和体内阻断 MM 的进展。相反，EIF3B 过表达增加了黑色素瘤细胞的细胞增殖和迁移。更重要的是，我们发现 EIF3B 在 MM 中的驱动作用是由 PTGS2 介导的。详细而言，我们发现 EIF3B 通过抑制 PTGS2 泛素化来稳定 PTGS2 表达，而 PTGS2 泛素化是由 E3 连接酶 MDM2 介导的。此外，与 EIF3B 一样，沉默PTGS2可以抑制MM的发展，更有趣的是，它可以逆转EIF3B在体外和体内过表达引起的情况。此外，EIF3B 沉默抑制的增殖和迁移也通过 PTGS2 的过表达得到部分恢复。总体而言，我们的研究结果揭示了 EIF3B 作为 MM 治疗靶标的潜力。鉴定 EIF3B 在 MM 中的功能可能为未来开发针对 MM 的更具体和更有效的靶向治疗策略铺平道路。我们的研究结果揭示了 EIF3B 作为 MM 治疗靶标的潜力。鉴定 EIF3B 在 MM 中的功能可能为未来开发针对 MM 的更具体和更有效的靶向治疗策略铺平道路。我们的研究结果揭示了 EIF3B 作为 MM 治疗靶标的潜力。鉴定 EIF3B 在 MM 中的功能可能为未来开发针对 MM 的更具体和更有效的靶向治疗策略铺平道路。