Upregulation of REV7 correlates with progression of malignant melanoma
Upregulation of REV7 correlates with progression of malignant melanoma
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DOI：
10.1111/pin.13174
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发表时间：
2021-10-12
影响因子：
2.2
通讯作者：
Murakumo, Yoshiki
中科院分区：
文献类型：
--
作者：
Hoshino, Akiyoshi;Nakayama, Chika;Murakumo, Yoshiki
REV 7是一种多功能蛋白，涉及DNA损伤耐受、细胞周期控制和基因表达，并参与多种人类肿瘤的致癌作用。据报道，REV 7表达与紫外线诱导的诱变有关;然而，REV 7表达在皮肤癌（包括恶性黑色素瘤）中的作用仍不清楚。在本研究中，我们研究了REV 7在恶性黑色素瘤中的临床和生物学意义。用免疫化学方法评价人皮肤癌中REV 7的表达水平。REV 7在恶性黑色素瘤、鳞状细胞癌和基底细胞癌中表达阳性。在三种皮肤癌中，REV 7免疫反应性增强与Ki-67标记指数评估的细胞增殖密切相关，在恶性黑色素瘤中与肿瘤厚度相关。恶性黑色素瘤细胞MEWO和G361中的REV 7缺失抑制细胞增殖、迁移和侵袭能力。REV 7缺失也影响MEWO细胞中细胞内信号分子AKT和ERK的表达，导致ERK信号激活下调。此外，在MEWO细胞中，REV 7耗竭促进了对顺铂的敏感性，但对达卡巴嗪不敏感。我们的研究结果表明，REV 7表达与恶性黑色素瘤的疾病进展相关。
REV7 is a multifunctional protein implicated in DNA damage tolerance, cell cycle control, and gene expression, and is involved in the carcinogenesis of various human tumors. It has been reported that REV7 expression is associated with ultraviolet-induced mutagenesis; however, the role of REV7 expression in skin cancers, including malignant melanomas, remains unclear. In the present study, we investigated the clinical and biological significance of REV7 in malignant melanoma. Levels of REV7 expression in human skin cancers were evaluated immunohistochemically. Positive expression of REV7 was frequently observed in malignant melanomas, as well as in squamous cell carcinomas and basal cell carcinomas. Enhanced immunoreactivity to REV7 was closely linked with cell proliferation assessed by Ki-67 labeling indexes in the three skin cancers, and was related with tumor thickness in malignant melanomas. REV7 depletion in malignant melanoma cells MEWO and G361 suppressed cell proliferation, migration, and invasion abilities. REV7 depletion also affected the expression of intracellular signaling molecules AKT and ERK in MEWO cells, resulting in downregulation of ERK signal activation. In addition, REV7 depletion facilitated sensitivity to cisplatin, but not to dacarbazine, in MEWO cells. Our results suggest that REV7 expression correlates with disease progression of malignant melanoma.