circHMCU Promotes Proliferation and Metastasis of Breast Cancer by Sponging the let-7 Family
circHMCU Promotes Proliferation and Metastasis of Breast Cancer by Sponging the let-7 Family
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circHMCU 通过支持 let-7 家族促进乳腺癌的增殖和转移
DOI：
10.1016/j.omtn.2020.03.014
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发表时间：
2020-06-05
影响因子：
8.8
通讯作者：
Yang, Qifeng
中科院分区：
文献类型：
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作者：
Song, Xiaojin;Liang, Yiran;Yang, Qifeng
环状RNA （Circular RNA, circRNA）作为一种新发现的非编码RNA，因其重要的生理和病理作用而成为人们关注的焦点。然而，circRNAs在调节癌症进展中的功能和机制在很大程度上是未知的。在本研究中，我们发现了一种称为circHMCU的circRNA，其表达与预后不良有关。它在具有高转移潜能的细胞系中与其亲代细胞系相比表达上调，在乳腺癌组织中与正常组织相比表达上调。体外实验证明，circHMCU通过影响G(1)期细胞周期检查点和上皮-间质转化（epithelial-mesenchymal transition， EMT）通路，显著促进乳腺癌细胞的增殖、迁移和侵袭能力。进一步的体内研究表明，circHMCU的过表达有助于乳腺癌的快速增殖和肺转移。为了确定其机制，生物信息学分析揭示了circHMCU中let-7 microRNAs的两个互补序列，并通过荧光素酶报告基因试验验证了这一点。最后，let-7 microRNAs可以通过抑制MCY、HMGA2和CCND1的表达来挽救circHMCU在乳腺癌中的功能。综上所述，我们的研究结果表明circHMCU在乳腺癌中具有致癌功能，可以作为乳腺癌诊断和预后的新生物标志物。
Circular RNA (circRNA), as a kind of novel identified non-coding RNA, has become the focus of attention for its vital physiological and pathological roles. However, the function and mechanism of circRNAs in the regulation of cancer progression are largely unknown. In the present study we found a circRNA termed circHMCU whose expression was associated with poor prognosis. It was upregulated in cell lines with high metastatic potential compared with its parental cell line and in breast cancer tissues compared with normal tissues. In vitro results proved that circHMCU could significantly promote proliferation, migration, and invasion abilities of breast cancer cells via affecting the G(1) phase cell cycle checkpoint and the epithelial-mesenchymal transition (EMT) pathway. Further in vivo studies showed that overexpression of circHMCU contributed to rapid proliferation and lung metastasis of breast cancer. For determination of the mechanisms, bioinformatics analysis revealed two complementary sequences within circHMCU for let-7 microRNAs, which was validated by a luciferase reporter assay. Finally, let-7 microRNAs could rescue the functions of circHMCU in breast cancer via suppressing the expression of MCY, HMGA2, and CCND1. Taken together, our findings demonstrated that circHMCU exerted oncogenic functions in breast cancer and could be a used as a novel biomarker in the diagnosis and prognosis of breast cancer.