Tumor suppressor function of miR-483-3p on squamous cell carcinomas due to its pro-apoptotic properties
Tumor suppressor function of miR-483-3p on squamous cell carcinomas due to its pro-apoptotic properties
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DOI：
10.4161/cc.25330
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发表时间：
2013-07-15
期刊：
影响因子：
4.3
通讯作者：
Rezzonico, Roger
中科院分区：
文献类型：
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作者：
Bertero, Thomas;Bourget-Ponzio, Isabelle;Rezzonico, Roger
许多癌症中miRNA表达的频繁改变，以及我们最近的报告显示miR-483 - 3p在皮肤伤口愈合的最后阶段的稳健积累，以及靶向CDC 25 A导致角质形成细胞增殖的停滞，使我们假设miR-483 - 3p也可以被赋予抗肿瘤特性。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来验证这一假设。miR-483 - 3p使SCC细胞对血清剥夺和药物诱导的凋亡敏感，从而发挥有效的肿瘤抑制活性。它的促凋亡活性是通过直接靶向几种抗凋亡基因如API 5、BIRC 5和RAN介导的。有趣的是，将miR-483 - 3p体内递送到皮下SCC异种移植物中显著阻碍了肿瘤生长。这种效应可以通过抑制细胞增殖和增加细胞凋亡来解释。这证明了其在以miR-483 - 3p下调为特征的许多癌症情况下进一步用作佐剂。
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.