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EIF3H 敲低通过调节细胞增殖、凋亡和细胞周期抑制恶性黑素瘤。

EIF3H knockdown inhibits malignant melanoma through regulating cell proliferation, apoptosis and cell cycle.

机构信息

Department of Dermatology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.

Department of Dermatology, The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.

出版信息

Exp Cell Res. 2021 May 1;402(1):112488. doi: 10.1016/j.yexcr.2021.112488. Epub 2021 Jan 26.

Abstract

Malignant melanoma (MM) causes 80% of skin cancer-related deaths and becomes the most lethal type of skin cancer. The molecular mechanism of MM is still not clear. This study aimed to reveal the relationship between MM and EIF3H. Clinical specimens were collected to preliminarily explore the role of EIF3H in MM. MM cell lines with EIF3H knockdown were constructed for investigating the effects of EIF3H on cell proliferation, apoptosis, cell cycle and cell motility. Mice xenograft model was constructed for verification in vivo. We found that EIF3H was obviously upregulated in MM tissues compared with normal skin tissues, which was correlated with tumor stage and risk of lymphatic metastasis. The in vitro results indicated that silencing EIF3H in MM cells could significantly suppress cell proliferation, promote cell apoptosis and induce cell cycle arrest. Moreover, EIF3H knockdown significantly restrained cell motility through regulating EMT-related proteins. The effects of EIF3H knockdown were also verified in mice xenograft model, which were represented by slower growth rate, smaller volume and lighter weight of tumors. Therefore, EIF3H was identified as a critical factor in the development and progression of MM which may be used as a novel therapeutic target in the treatment of MM.

摘要

恶性黑色素瘤(MM)导致 80%的皮肤癌相关死亡,是最致命的皮肤癌类型。MM 的分子机制尚不清楚。本研究旨在揭示 MM 与 EIF3H 之间的关系。收集临床标本初步探讨 EIF3H 在 MM 中的作用。构建了 EIF3H 敲低的 MM 细胞系,用于研究 EIF3H 对细胞增殖、凋亡、细胞周期和细胞迁移的影响。构建了小鼠异种移植模型进行体内验证。我们发现,与正常皮肤组织相比,MM 组织中 EIF3H 明显上调,与肿瘤分期和淋巴转移风险相关。体外结果表明,沉默 MM 细胞中的 EIF3H 可显著抑制细胞增殖,促进细胞凋亡并诱导细胞周期停滞。此外,EIF3H 敲低通过调节 EMT 相关蛋白显著抑制细胞迁移。EIF3H 敲低的效果也在小鼠异种移植模型中得到了验证,表现为肿瘤生长速度较慢、体积较小和重量较轻。因此,EIF3H 被确定为 MM 发生和发展的关键因素,它可能成为 MM 治疗的新的治疗靶点。

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