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长链非编码 RNA HOTAIR 作为 ceRNA 与乳腺癌风险和预后相关。

LncRNA HOTAIR as a ceRNA is related to breast cancer risk and prognosis.

机构信息

Department of Surgical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China.

Department of Breast and Thyroid Surgery, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China.

出版信息

Breast Cancer Res Treat. 2023 Aug;200(3):375-390. doi: 10.1007/s10549-023-06982-4. Epub 2023 Jun 9.

Abstract

PURPOSE

Breast cancer (BC) is one of the biggest threats to women's health. LncRNA HOTAIR is related to the recurrence and metastasis of BC. Whether HOTAIR can serve as an effective biomarker to distinguish BC patients with different prognosis need to be further studied.

METHODS

The miRNA and mRNA expression profile data of BC patients were downloaded from TCGA database. Univariate Cox regression was used to screen differential expression genes (DEGs). The miRcode database and miRWalk database were used to predict miRNA binding to HOTAIR and binding sites of miRNAs, respectively. Kaplan-Meier (KM) analysis was used to estimate the overall survival rate of BC patients. Finally, qRT-PCR and western blot were applied to evaluate the expression level of HOTAIR and mRNAs between BC cells and normal mammary cells.

RESULTS

The patients with high HOTAIR expression had poor prognosis in BC. Totally 10 genes correlated with BC prognosis were identified from 170 DEGs, among which PAX7, IYD, ZIC2, MS4A1, TPRXL, CD24, LHX1 were positively correlated with HOTAIR, while CHAD, NPY1R, TPRG1 were opposite. The levels of IYD, ZIC2, CD24 mRNA and protein were increased in BC tissues and BC cells. In BC cells, the levels of IYD, ZIC2 and CD24 mRNA and protein were significantly increased in HOTAIR overexpressed group. HOTAIR had the strongest interaction with hsa-miR-129-5p, followed by hsa-miR-107.

CONCLUSION

HOTAIR regulated the expression of downstream genes by interacting with 8 miRNAs and ultimately affected the prognosis of BC patients.

摘要

目的

乳腺癌(BC)是威胁女性健康的最大因素之一。长链非编码 RNA HOTAIR 与 BC 的复发和转移有关。HOTAIR 是否可以作为区分预后不同的 BC 患者的有效生物标志物,需要进一步研究。

方法

从 TCGA 数据库下载 BC 患者的 miRNA 和 mRNA 表达谱数据。使用单因素 Cox 回归筛选差异表达基因(DEGs)。使用 miRcode 数据库和 miRWalk 数据库分别预测 miRNA 与 HOTAIR 的结合以及 miRNA 的结合位点。Kaplan-Meier(KM)分析用于估计 BC 患者的总生存率。最后,qRT-PCR 和 Western blot 用于评估 BC 细胞和正常乳腺细胞中 HOTAIR 和 mRNAs 的表达水平。

结果

高 HOTAIR 表达的 BC 患者预后不良。从 170 个 DEGs 中鉴定出与 BC 预后相关的 10 个基因,其中 PAX7、IYD、ZIC2、MS4A1、TPRXL、CD24、LHX1 与 HOTAIR 呈正相关,而 CHAD、NPY1R、TPRG1 则相反。BC 组织和 BC 细胞中 IYD、ZIC2、CD24 mRNA 和蛋白水平升高。在 BC 细胞中,HOTAIR 过表达组中 IYD、ZIC2 和 CD24 mRNA 和蛋白水平显著升高。HOTAIR 与 hsa-miR-129-5p 的相互作用最强,其次是 hsa-miR-107。

结论

HOTAIR 通过与 8 个 miRNA 相互作用调节下游基因的表达,最终影响 BC 患者的预后。

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