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绿茶多酚通过调节circ_MITF/miR-30e-3p/HDAC2轴抑制恶性黑色素瘤进展。

Green tea polyphenols inhibit malignant melanoma progression via regulating circ_MITF/miR-30e-3p/HDAC2 axis.

作者信息

Wu Kejia, Wei Yuegang, Yu Ye, Shan Minjie, Tang Ye, Sun Yan

机构信息

Department of Dermatology, Changzhou Hospital of Traditional Chinese Medicine, Changzhou, China.

Department of Dermatology, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China.

出版信息

Biotechnol Appl Biochem. 2022 Apr;69(2):808-821. doi: 10.1002/bab.2153. Epub 2021 Jul 22.

Abstract

Green tea polyphenols (GTPs) are regarded as anticancer substances and have been revealed to play significant roles in the development of malignant melanoma. However, the mechanisms by which GTPs perform anticarcinogenic activity are not well elucidated. Cellular function assays revealed that GTPs inhibited melanoma cell proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and promoted apoptosis in vitro. Circ_MITF expression was elevated in melanoma tissues and cells but was decreased by GTPs in cells. Functional experiments indicated circ_MITF overexpression reversed the anticancer effects of GTPs on melanoma cells. Then the underlying mechanism analysis suggested that circ_MITF served as a sponge for miR-30e-3p to upregulate the level of HDAC2. MiR-30e-3p reexpression attenuated the regulatory effects of circ_MITF on GTPs-treated melanoma cells. Silencing of miR-30e-3p promoted the malignant phenotypes in GTPs-treated melanoma cells, which were reversed by HDAC2 knockdown. Preclinically, administration of GTPs suppressed the expression of downstream target genes and repressed tumorigenesis of xenografts in nude mice. In all, GTPs suppressed melanoma progression by regulating circ_MITF/miR-30e-3p/HDAC2 axis, providing a potential therapeutic strategy for human malignant melanoma intervention.

摘要

绿茶多酚(GTPs)被视为抗癌物质,并且已被揭示在恶性黑色素瘤的发展中发挥重要作用。然而,GTPs发挥抗癌活性的机制尚未得到充分阐明。细胞功能测定表明,GTPs在体外抑制黑色素瘤细胞的增殖、迁移、侵袭、上皮-间质转化(EMT),并促进细胞凋亡。Circ_MITF在黑色素瘤组织和细胞中表达升高,但在细胞中被GTPs降低。功能实验表明,circ_MITF过表达逆转了GTPs对黑色素瘤细胞的抗癌作用。随后的潜在机制分析表明,circ_MITF作为miR-30e-3p的海绵,上调HDAC2的水平。miR-30e-3p的重新表达减弱了circ_MITF对GTPs处理的黑色素瘤细胞的调节作用。miR-30e-3p的沉默促进了GTPs处理的黑色素瘤细胞中的恶性表型,而HDAC2的敲低则逆转了这些表型。临床前研究表明,给予GTPs可抑制裸鼠异种移植瘤下游靶基因的表达并抑制其肿瘤发生。总之,GTPs通过调节circ_MITF/miR-30e-3p/HDAC2轴抑制黑色素瘤进展,为人类恶性黑色素瘤的干预提供了一种潜在的治疗策略。

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