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LINC01857 作为一种致癌基因,通过与乳腺癌中的 CREBBP 相互作用来调节 CREB1 的激活。

LINC01857 as an oncogene regulates CREB1 activation by interacting with CREBBP in breast cancer.

机构信息

Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Department of Thyroid Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

出版信息

J Cell Physiol. 2019 Aug;234(8):14031-14039. doi: 10.1002/jcp.28090. Epub 2019 Jan 9.

Abstract

Breast cancer is a one of the most malignant threats among women worldwide. However, the mechanism underlying breast cancer development remains unclear. Long noncoding RNAs (lncRNAs) have been reported to participate in breast cancer. Whether lncRNA LINC01857 is involved in breast cancer requires investigation. In this study, we found that LINC01857 was highly expressed in breast cancer tissues and cells (p < 0.05). High LINC01857 expression predicted poor prognosis in breast cancer patients. Functionally, LINC01857 silencing impaired proliferation and enhanced apoptosis of breast cancer cells ( p < 0.05). Decreased LINC01857 inhibited breast cancer cells migration and invasion ability ( p < 0.05). In terms of mechanism, LINC01857 promoted H3K27Ac deposition on CREB1 promoter and initiated its transcription by recruiting CREBBP. Overexpression of CREB1 reversed the biological behavior of breast cancer cells induced by LINC01857 silencing ( p < 0.05). Taken together, our findings demonstrated that LINC01857 promoted breast cancer development by promoting H3K27Ac and CREB1 transcription via enhancing CREBBP enrichment in the CREB1 promoter region.

摘要

乳腺癌是全球女性最恶性的威胁之一。然而,乳腺癌发展的机制仍不清楚。长链非编码 RNA(lncRNA)已被报道参与乳腺癌。lncRNA LINC01857 是否参与乳腺癌需要进一步研究。在本研究中,我们发现 LINC01857 在乳腺癌组织和细胞中高表达(p<0.05)。高表达的 LINC01857 预测乳腺癌患者预后不良。功能上,LINC01857 沉默抑制乳腺癌细胞的增殖并增强细胞凋亡(p<0.05)。下调 LINC01857 抑制乳腺癌细胞迁移和侵袭能力(p<0.05)。在机制方面,LINC01857 通过募集 CREBBP 促进 H3K27Ac 在 CREB1 启动子上的沉积,从而启动其转录。过表达 CREB1 逆转了 LINC01857 沉默诱导的乳腺癌细胞的生物学行为(p<0.05)。综上所述,我们的研究结果表明,LINC01857 通过增强 CREBBP 在 CREB1 启动子区域的富集,促进 H3K27Ac 和 CREB1 转录,从而促进乳腺癌的发展。

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