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miR-33a-5p 通过靶向 SNAI2 抑制黑色素瘤细胞的生长和转移。

MiR-33a-5p inhibits the growth and metastasis of melanoma cells by targeting SNAI2.

机构信息

Department of Plastic Surgery, The Affiliated Hospital of Beihua University, Jilin, China.

出版信息

Neoplasma. 2020 Jul;67(4):813-824. doi: 10.4149/neo_2020_190823N811. Epub 2020 Apr 16.

Abstract

MicroRNAs have been verified as critical regulators in the development of melanoma. miR-33a-5p was significantly downregulated in melanoma, however, the specific role and regulatory mechanism of miR-33a-5p in melanoma were still unclear. The present study identified that miR-33a-5p was downregulated in melanoma tissues and cells, while SNAI2 was upregulated. miR-33a-5p directly targeted SNAI2 and negatively regulated its expression in melanoma cells. Overexpression of miR-33a-5p repressed proliferation, migration, invasion, EMT and promoted apoptosis of melanoma cell in vitro, these effects were partially reversed by SNAI2 overexpression. In addition, miR-33a-5p impaired melanoma growth in vivo by inhibiting SNAI2. Mechanistically, miR-33a-5p repressed activation of the PI3K/AKT/mTOR pathway by targeting SNAI2. In conclusion, miR-33a-5p repressed the progression of melanoma by targeting SNAI2 via inactivation of the PI3K/AKT/mTOR signaling pathway, providing a potential molecular mechanism for the treatment of melanoma.

摘要

MicroRNAs 已被证实为黑色素瘤发展的关键调控因子。miR-33a-5p 在黑色素瘤中显著下调,然而,miR-33a-5p 在黑色素瘤中的具体作用和调控机制仍不清楚。本研究表明 miR-33a-5p 在黑色素瘤组织和细胞中下调,而 SNAI2 上调。miR-33a-5p 可直接靶向 SNAI2,并负调控其在黑色素瘤细胞中的表达。miR-33a-5p 的过表达抑制黑色素瘤细胞的体外增殖、迁移、侵袭、EMT,并促进其凋亡,而过表达 SNAI2 可部分逆转这些作用。此外,miR-33a-5p 通过抑制 SNAI2 抑制黑色素瘤在体内的生长。机制上,miR-33a-5p 通过靶向 SNAI2 抑制 PI3K/AKT/mTOR 通路的激活。综上所述,miR-33a-5p 通过抑制 PI3K/AKT/mTOR 信号通路失活来抑制 SNAI2,从而抑制黑色素瘤的进展,为黑色素瘤的治疗提供了潜在的分子机制。

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