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长链非编码 RNA MIF-AS1 通过调控 miR-1249-3p/HOXB8 轴促进乳腺癌细胞的增殖、迁移和 EMT 过程。

Long non-coding RNA MIF-AS1 promotes breast cancer cell proliferation, migration and EMT process through regulating miR-1249-3p/HOXB8 axis.

机构信息

Department of Thyroid and Breast, Ningbo Medical Center Lihuili Eastern Hospital/Taipei Medical University Ningbo Medical Center, Ningbo, Zhejiang Province, 315000, China.

Department of Thyroid and Breast, Ningbo Medical Center Lihuili Eastern Hospital/Taipei Medical University Ningbo Medical Center, Ningbo, Zhejiang Province, 315000, China.

出版信息

Pathol Res Pract. 2019 Jul;215(7):152376. doi: 10.1016/j.prp.2019.03.005. Epub 2019 May 4.

Abstract

Breast cancer (BC) is one of the leading cause of cancer-related death among females worldwide. Mounting evidences indicate that long non-coding RNAs (lncRNAs) were involved in tumor progression by acting as either oncogenes or tumor suppressors in multiple cancers. In this study, we focused on the function and mechanism of lncRNA Migration Inhibitory Factor Antisense RNA 1 (MIF-AS1) in BC. qRT-PCR showed that MIF-AS1 was upregulated in BC tissues and cells. To detect its bio-function, a series of loss-of-function assays were carried out. Thereafter, we found that MIF-AS1 depletion inhibited BC cell proliferation, migration and epithelial-mesenchymal transition (EMT). Recently, increasing studies indicate that lncRNAs can function as competing endogenous RNAs (ceRNAs). Using bioinformatics analysis and luciferase reporter assay, we identified that MIF-AS1 regulated the level of Homeobox B8 (HOXB8) via binding to miR-1249-3p. Taken all together, our findings proved that MIF-AS1 acted as a ceRNA by modulating miR-1249-3p/HOXB8 axis in breast cancer. LncRNA MIF-AS1 might be a new biomarker and therapeutic target for BC patients.

摘要

乳腺癌(BC)是全球女性癌症相关死亡的主要原因之一。越来越多的证据表明,长非编码 RNA(lncRNA)在多种癌症中可以作为癌基因或肿瘤抑制因子参与肿瘤进展。在本研究中,我们专注于 lncRNA 迁移抑制因子反义 RNA 1(MIF-AS1)在 BC 中的功能和机制。qRT-PCR 显示 MIF-AS1 在 BC 组织和细胞中上调。为了检测其生物功能,进行了一系列的功能丧失实验。此后,我们发现 MIF-AS1 耗竭抑制了 BC 细胞的增殖、迁移和上皮-间充质转化(EMT)。最近,越来越多的研究表明,lncRNA 可以作为竞争性内源 RNA(ceRNA)发挥作用。通过生物信息学分析和荧光素酶报告基因实验,我们确定 MIF-AS1 通过与 miR-1249-3p 结合来调节 Homeobox B8(HOXB8)的水平。综上所述,我们的研究结果证明 MIF-AS1 通过调节 miR-1249-3p/HOXB8 轴在乳腺癌中发挥 ceRNA 作用。LncRNA MIF-AS1 可能是 BC 患者的新生物标志物和治疗靶点。

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