A novel long non-coding RNA AC073352.1 promotes metastasis and angiogenesis via interacting with YBX1 in breast cancer.

A novel long non-coding RNA AC073352.1 promotes metastasis and angiogenesis via interacting with YBX1 in breast cancer.
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DOI:
10.1038/s41419-021-03943-x
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发表时间:
2021-07-03
影响因子:
9
通讯作者:
Wang C
Wang C
中科院分区:
生物学1区
文献类型:
--
作者:
Kong X;Li J;Li Y;Duan W;Qi Q;Wang T;Yang Q;Du L;Mao H;Wang C

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乳腺癌是全球女性癌症死亡的主要原因。转移患者预后较差,乳腺癌转移机制尚不完全清楚。长非编码RNA(LncRNAs)在乳腺癌的发生发展中起着至关重要的作用。然而,lncRNA驱动乳腺癌转移的潜在机制尚不清楚。本论文的主要目的是探索一种具有功能的LncRNA及其在乳腺癌中的作用机制。在这里,我们发现了一种新的lncRNA AC073352.1,它在乳腺癌组织中显著上调,并与乳腺癌患者的晚期TNM分期和不良预后有关。此外,还发现AC073352.1在体外能促进乳腺癌细胞的迁移和侵袭,在体内能促进乳腺癌的转移。我们从机制上阐明了AC073352.1与YBX1相互作用并稳定了其蛋白表达。下调YBX1基因可减少乳腺癌细胞的迁移和侵袭,并可部分逆转AC073352.1过表达对乳腺癌转移的促进作用。此外,AC073352.1可能通过与乳腺癌细胞中的YBX1结合而包装成外切体,从而导致血管生成。综上所述,我们的结果表明,AC073352.1通过结合YBX1促进乳腺癌的转移和血管生成,有望成为一种新的乳腺癌预后生物标志物和治疗靶点。
Breast cancer is the major cause of cancer death worldwide in women. Patients with metastasis have poor prognosis and the mechanisms of breast cancer metastasis are not completely understood. Long non-coding RNAs (lncRNAs) have been shown to have crucial roles in breast cancer development and progression. However, the underlying mechanisms by which lncRNA-driven breast cancer metastasis are unknown. The main objective of this paper is to explore a functional lncRNA and its mechanisms in breast cancer. Here we identified a novel lncRNA AC073352.1 that was significantly upregulated in breast cancer tissues and was associated with advanced TNM stages and poor prognosis in breast cancer patients. In addition, AC073352.1 was found to promote the migration and invasion of breast cancer cells in vitro and enhance breast cancer metastasis in vivo. Mechanistically, we elucidated that AC073352.1 interacted with YBX1 and stabilized its protein expression. Knock down of YBX1 reduced breast cancer cell migration and invasion and could partially reverse the stimulative effects of AC073352.1 overexpressed on breast cancer metastasis. Moreover, AC073352.1 might be packaged into exosomes by binding to YBX1 in breast cancer cells resulting in angiogenesis. Collectively, our results demonstrated that AC073352.1 promoted breast cancer metastasis and angiogenesis via binding YBX1, and it could serve as a promising, novel biomarker for prognosis and a therapeutic target in breast cancer.
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