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首页> 外文期刊>Cell cycle >Tumor suppressor function of miR-483-3p on squamous cell carcinomas due to its pro-apoptotic properties
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Tumor suppressor function of miR-483-3p on squamous cell carcinomas due to its pro-apoptotic properties

机译：由于miR-483-3p的促凋亡特性，其在鳞状细胞癌中具有抑癌功能

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摘要

The frequent alteration of miRNA expression in many cancers, together with our recent reports showing a robust accumulation of miR-483-3p at the final stage of skin wound healing, and targeting of CDC25A leading to an arrest of keratinocyte proliferation, led us to hypothesize that miR-483-3p could also be endowed with antitumoral properties. We tested that hypothesis by documenting the in vitro and in vivo impacts of miR-483-3p in squamous cell carcinoma (SCC) cells. miR-483-3p sensitized SCC cells to serum deprivation- and drug-induced apoptosis, thus exerting potent tumor suppressor activities. Its pro-apoptotic activity was mediated by a direct targeting of several anti-apoptotic genes, such as API5, BIRC5, and RAN. Interestingly, an in vivo delivery of miR-483-3p into subcutaneous SCC xenografts significantly hampered tumor growth. This effect was explained by an inhibition of cell proliferation and an increase of apoptosis. This argues for its further use as an adjuvant in the many instances of cancers characterized by a downregulation of miR-483-3p.
机译：在许多癌症中，miRNA表达的频繁改变，加上我们最近的报道显示，miR-483-3p在皮肤伤口愈合的最后阶段大量积累，靶向CDC25A导致角质形成细胞增殖被阻止，这使我们做出了假设miR-483-3p也可以具有抗肿瘤特性。我们通过记录miR-483-3p在鳞状细胞癌（SCC）细胞中的体外和体内影响，测试了该假设。 miR-483-3p使SCC细胞对血清剥夺和药物诱导的细胞凋亡敏感，从而发挥有效的抑癌活性。它的促凋亡活性是通过直接靶向几种抗凋亡基因，例如API5，BIRC5和RAN介导的。有趣的是，将miR-483-3p体内递送至皮下SCC异种移植物中显着阻碍了肿瘤的生长。抑制细胞增殖和增加细胞凋亡可以解释这种作用。这证明了其在许多以miR-483-3p下调为特征的癌症中作为佐剂的进一步用途。

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