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长非编码 RNA p10247,在乳腺癌中高表达(lncRNA-BCHE),与转移相关。

Long non-coding RNA p10247, high expressed in breast cancer (lncRNA-BCHE), is correlated with metastasis.

机构信息

Department of Medical Genetics, School of Basic Medical Sciences, Peking University, Beijing, China.

Key Laboratory of Birth Defects and Reproductive Health of the National Health and Family Planning Commission, Chongqing Population and Family Planning Science and Technology Research Institute, Chongqing, China.

出版信息

Clin Exp Metastasis. 2018 Mar;35(3):109-121. doi: 10.1007/s10585-018-9901-2. Epub 2018 Jun 8.

Abstract

Recent studies have shown that long non-coding RNAs (lncRNAs) have key functions during breast cancer development. Considering the complexity of IncRNAs regulatory network, the identification of novel and functional lncRNAs associated with breast cancer is thus very important. By using Agilent LncRNA Human Gene Expression Microarray, we identified a number of lncRNAs that were differentially expressed in breast cancer compared to their corresponding adjacent tissues. According to the microarray, the expression of p10247, henceforth named as lncRNA-BCHE (standing for lncRNA high expressed in breast cancer), was found to be uniformly higher in all the five breast cancer tissues tested, and this was further confirmed in 56 breast cancer tissues by real-time RT-PCR. The function of lncRNA-BCHE in breast cancer cells was tested by knockdown and over-expression experiments in vitro. We also analyzed the public cohorts of breast cancer patients on the Kaplan Meier plotter platform. Clinical analysis revealed that the expression of lncRNA-BCHE was significantly correlated with advanced clinical stage and lymph node metastasis. Our data indicate that lncRNA-BCHE regulates the growth, migration and invasion of breast cancer cells. In addition, we found that these functions are mediated, at least in part, by the regulation of integrin subunit beta 1 (ITGB1) levels. The expression of ITGB1 serves as a negative prognostic factor and metastasis risk predictor in breast cancer, irrespective of subtype and therapeutic regimen. In summary, our results suggest that lncRNA-BCHE is an oncogenic lncRNA enhancing the growth and metastatic potential of breast cancer cells, and a potential predictor of breast cancer metastatic progression.

摘要

最近的研究表明,长非编码 RNA(lncRNAs)在乳腺癌发展过程中具有关键功能。鉴于 IncRNA 调控网络的复杂性,因此鉴定与乳腺癌相关的新型和功能性 lncRNA 非常重要。我们使用 Agilent LncRNA Human Gene Expression Microarray,鉴定了一些在乳腺癌与相应相邻组织相比差异表达的 lncRNAs。根据微阵列,p10247 的表达,此后命名为 lncRNA-BCHE(代表在乳腺癌中高表达的 lncRNA),在所有测试的五例乳腺癌组织中均均匀升高,这在 56 例乳腺癌组织中通过实时 RT-PCR 进一步证实。通过体外敲低和过表达实验测试了 lncRNA-BCHE 在乳腺癌细胞中的功能。我们还在 Kaplan Meier plotter 平台上分析了公共乳腺癌患者队列。临床分析表明,lncRNA-BCHE 的表达与晚期临床分期和淋巴结转移明显相关。我们的数据表明,lncRNA-BCHE 调节乳腺癌细胞的生长、迁移和侵袭。此外,我们发现这些功能至少部分是通过整合素亚基β1(ITGB1)水平的调节介导的。ITGB1 的表达是乳腺癌的一个负预后因素和转移风险预测因子,与亚型和治疗方案无关。总之,我们的结果表明,lncRNA-BCHE 是一种致癌 lncRNA,可增强乳腺癌细胞的生长和转移潜能,是乳腺癌转移进展的潜在预测因子。

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