新型预后标志物 SPOCK2 可调控黑色素瘤的肿瘤进展。

IF 3.5 3区 医学 Q1 DERMATOLOGY
Ji Young Kang, Hyeijin Cho, Minchan Gil, Haeryung Lee, Soochul Park, Kyung Eun Kim
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引用次数: 0

摘要

富含酸性和半胱氨酸的分泌蛋白/osteonectin、cwcv和kazal样结构域蛋白多糖2(SPOCK2)是一种调节细胞分化和生长的蛋白质。最近有研究报告称,SPOCK2 在多种人类癌症的进展过程中发挥着重要作用;然而,SPOCK2 在黑色素瘤中的作用仍然未知。因此,本研究探讨了SPOCK2在黑色素瘤进展中的作用及相关机制。为了评估SPOCK2在黑色素瘤患者中表达的临床意义,我们采用系统的多组学分析方法分析了SPOCK2表达与黑色素瘤患者预后价值之间的关联。随后,为了研究 Spock2 在黑色素瘤体外和体内进展过程中的作用,我们敲除了 B16F10 黑色素瘤细胞系中的 Spock2。高水平的SPOCK2与黑色素瘤患者的良好预后和长期生存率呈正相关。Spock2基因敲除通过诱导细胞周期和抑制细胞凋亡促进黑色素瘤细胞增殖。此外,通过上调 MMP2 和 MT1-MMP,下调 Spock2 能显著增加细胞的迁移和侵袭。MAPK抑制剂抑制了细胞增殖和迁移的增加,而Spock2敲除细胞的ERK磷酸化明显增强。因此,Spock2 可作为肿瘤抑制基因,通过调节 MAPK/ERK 信号通路来调控黑色素瘤的进展。此外,与对照组相比,Spock2敲除细胞注射在C57BL6小鼠体内诱导了大量肿瘤生长和肺转移。我们的研究结果表明,SPOCK2在黑色素瘤的恶性进展中起着关键作用,是黑色素瘤的一个新的治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The novel prognostic marker SPOCK2 regulates tumour progression in melanoma

Secreted protein acidic and cysteine rich/osteonectin, cwcv and kazal-like domain proteoglycan 2 (SPOCK2) is a protein that regulates cell differentiation and growth. Recent studies have reported that SPOCK2 plays important roles in the progression of various human cancers; however, the role of SPOCK2 in melanoma remains unknown. Therefore, this study investigated the roles of SPOCK2 and the related mechanisms in melanoma progression. To evaluate the clinical significance of SPOCK2 expression in patients with melanoma, we analysed the association between SPOCK2 expression and its prognostic value for patients with melanoma using systematic multiomic analysis. Subsequently, to investigate the roles of Spock2 in melanoma progression in vitro and in vivo, we knocked down Spock2 in the B16F10 melanoma cell line. High SPOCK2 levels were positively associated with good prognosis and long survival rate of patients with melanoma. Spock2 knockdown promoted melanoma cell proliferation by inducing the cell cycle and inhibiting apoptosis. Moreover, Spock2 downregulation significantly increased cell migration and invasion by upregulating MMP2 and MT1-MMP. The increased cell proliferation and migration were inhibited by MAPK inhibitor, and ERK phosphorylation was considerably enhanced in Spock2 knockdown cells. Therefore, Spock2 could function as a tumour suppressor gene to regulate melanoma progression by regulating the MAPK/ERK signalling pathway. Additionally, Spock2 knockdown cell injection induced considerable tumour growth and lung metastasis in C57BL6 mice compared to that in the control group. Our findings suggest that SPOCK2 plays crucial roles in malignant progression of melanoma and functions as a novel therapeutic target of melanoma.

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来源期刊
Experimental Dermatology
Experimental Dermatology 医学-皮肤病学
CiteScore
6.70
自引率
5.60%
发文量
201
审稿时长
2 months
期刊介绍: Experimental Dermatology provides a vehicle for the rapid publication of innovative and definitive reports, letters to the editor and review articles covering all aspects of experimental dermatology. Preference is given to papers of immediate importance to other investigators, either by virtue of their new methodology, experimental data or new ideas. The essential criteria for publication are clarity, experimental soundness and novelty. Letters to the editor related to published reports may also be accepted, provided that they are short and scientifically relevant to the reports mentioned, in order to provide a continuing forum for discussion. Review articles represent a state-of-the-art overview and are invited by the editors.
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