Circular RNA circBCBM1 promotes breast cancer brain metastasis by modulating miR-125a/BRD4 axis.
Circular RNA circBCBM1 promotes breast cancer brain metastasis by modulating miR-125a/BRD4 axis.
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DOI：
10.7150/ijbs.58916
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发表时间：
2021
影响因子：
9.2
通讯作者：
An M
中科院分区：
文献类型：
--
作者：
Fu B;Liu W;Zhu C;Li P;Wang L;Pan L;Li K;Cai P;Meng M;Wang Y;Zhang A;Tang W;An M
环状RNA(CircRNAs)在肿瘤的发生和各种癌症的进展中起着关键作用。我们以前发现了一个新的上调的CircRNA，CircBCBM1(HSA_CIRC_0001944)，在乳腺癌脑转移的背景下。然而，CircBCBM1在乳腺癌脑转移中的潜在生物学功能和分子机制仍很不清楚。在本研究中，我们证实了CircBCBM1是一种稳定的细胞质CircRNA。在功能上，CircBCBM1在体外促进231-BR细胞的增殖和迁移，在体内促进肿瘤生长和脑转移。在机制上，CircBCBM1作为内源性miR-125a海绵抑制miR-125a活性，导致BRD4(含溴结构域4)上调，继而通过Sonic hedgehog(SHH)信号通路上调MMP9(基质金属肽酶9)。重要的是，在乳腺癌脑转移细胞、临床组织和血浆标本中，CircBCBM1显著上调；此外，在原发癌组织中过表达与乳腺癌患者较短的脑无转移生存期(BMFS)有关。这些发现表明，CircBCBM1通过CircBCBM1/miR-125a/BRD4轴参与乳腺癌脑转移。CircBCBM1可能成为乳腺癌脑转移的一种新的诊断和预后的生物标志物和潜在的治疗靶点。
Circular RNAs (circRNAs) play critical roles in tumorigenesis and the progression of various cancers. We previously identified a novel upregulated circRNA, circBCBM1 (hsa_circ_0001944), in the context of breast cancer brain metastasis. However, the potential biological function and molecular mechanism of circBCBM1 in breast cancer brain metastasis remain largely unknown. In this study, we confirmed that circBCBM1 was a stable and cytoplasmic circRNA. Functionally, circBCBM1 promoted the proliferation and migration of 231-BR cells in vitro and growth and brain metastasis in vivo. Mechanistically, circBCBM1 acted as an endogenous miR-125a sponge to inhibit miR-125a activity, resulting in the upregulation of BRD4 (bromodomain containing 4) and subsequent upregulation of MMP9 (matrix metallopeptidase 9) through Sonic hedgehog (SHH) signaling pathway. Importantly, circBCBM1 was markedly upregulated in the breast cancer brain metastasis cells and clinical tissue and plasma samples; besides, circBCBM1 overexpression in primary cancerous tissues was associated with shorter brain metastasis-free survival (BMFS) of breast cancer patients. These findings indicate that circBCBM1 is involved in breast cancer brain metastasis via circBCBM1/miR-125a/BRD4 axis. CircBCBM1 may serve as a novel diagnostic and prognostic biomarker and potential therapeutic target for breast cancer brain metastasis.
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DOI：
10.1016/j.bbcan.2016.12.001
发表时间：
2017-01
期刊：
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影响因子：
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