Cip2a/miR-301a feedback loop promotes cell proliferation and invasion of triple-negative breast cancer
Cip2a/miR-301a feedback loop promotes cell proliferation and invasion of triple-negative breast cancer
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Cip2a/miR-301a反馈环促进三阴性乳腺癌细胞增殖和侵袭
DOI：
10.7150/jca.35704
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发表时间：
2019-01-01
影响因子：
3.9
通讯作者：
Liu, Hao
中科院分区：
文献类型：
--
作者：
Yin, Jiang;Chen, Danyang;Liu, Hao
三阴性乳腺癌（TNBC）是一种高度侵略性的乳腺癌亚型，缺乏有效的靶向疗法。蛋白质磷酸酶2a（CIP2A）的癌性抑制剂是一种癌基因，已知可以抑制人类恶性肿瘤中PP2A肿瘤抑制活性。我们先前证明CIP2A是治疗TNBC的新目标。但是，CIP2A在TNBC进程中的功能作用仍未完全表征。在这项研究中，我们确定miR-301a通过miRNA微阵列分析是TNBC细胞系中CIP2A的新靶标。我们发现CIP2A增加了E2F1的表达，从而通过占据miR-301a宿主基因SKA2启动子来转录激活miR-301a。此外，我们发现TNBC组织中miR-301a水平显着增加，而miR-301a的上调负责CIP2A诱导的细胞增殖和TNBC细胞的侵袭。此外，miR-301a反馈通过激活ERK/CREB信号传导促进CIP2A的表达。我们的研究一起表明，CIP2A和miR-301a之间的自动调节反馈回路，此自动调节环可能在TNBC进展中起重要作用。
Triple-negative breast cancer (TNBC) is a highly aggressive breast cancer subtype and lacks effective targeted therapies. Cancerous inhibitor of protein phosphatase 2A (Cip2a) is an oncogene that is known to inhibit PP2A tumor suppressor activity in human malignancies. We previously demonstrated that Cip2a is a novel target for the treatment of TNBC. However, the functional roles of Cip2a in TNBC progression are still not fully characterized. In this study, we identified that miR-301a is a novel target of Cip2a in TNBC cell lines by miRNA microarray analysis. We found that Cip2a increases E2F1 expression, which in turn transcriptional activates miR-301a by occupying the miR-301a host gene SKA2 promoter. Moreover, we found that miR-301a level is significantly increased in TNBC tissues, and up-regulation of miR-301a is responsible for Cip2a-induced cell proliferation and invasion of TNBC cells. Furthermore, miR-301a feedback promotes the expression of Cip2a via activation of ERK/CREB signaling. Together, our study suggests an auto-regulatory feedback loop between Cip2a and miR-301a and this auto-regulatory loop might play an important role in TNBC progression.