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长链非编码RNA RHPN1-AS1的沉默抑制上皮-间质转化并抑制乳腺癌进展。

Silencing of the long non-coding RNA RHPN1-AS1 suppresses the epithelial-to-mesenchymal transition and inhibits breast cancer progression.

作者信息

Zheng Shipeng, Lv Peihua, Su Jing, Miao Keke, Xu Han, Li Mengquan

机构信息

Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University Zhengzhou 450052, China.

Key Laboratory of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University Zhengzhou 450052, China.

出版信息

Am J Transl Res. 2019 Jun 15;11(6):3505-3517. eCollection 2019.

Abstract

Breast cancer (BC) is a frequently diagnosed malignancy in women. Increasing evidence implicates mis-expression of the long non-coding RNA (lncRNA) RHPN1 antisense RNA 1 (RHPN1-AS1) in the development of multiple cancer types. However, little is known about the expression pattern and function of lncRNA RHPN1-AS1 in the pathobiology of BC. We evaluated the expression of RHPN1-AS1 in The Cancer Genome Atlas dataset, and analyzed associations between RHPN1-AS1 expression and clinicopathologic features of BC patients. Additionally, we compared the expression of RHPN1-AS1 between BC and breast non-tumor samples via quantitative real-time polymerase chain reaction, and in situ hybridization, and evaluated the prognostic value of RHPN1-AS1 in a BC tissue microarray. We examined the impact of RHPN1-AS1 knockdown on proliferation, migration, and invasion of BC cells , and tumor growth . Bioinformatics analyses were used to predict the function of RHPN1-AS1 in BC. RHPN1-AS1 expression was upregulated in BC and elevated RHPN1-AS1 expression was strongly associated with poor prognosis of BC patients. Moreover, both univariate and multivariate analyses revealed that RHPN1-AS1 was a significant and independent predictor of BC prognosis. Functionally, RHPN1-AS1 silencing attenuated BC cell proliferation, migration, and invasion , and reduced tumor growth in xenograft models. Furthermore, RHPN1-AS1 silencing was associated with a decrease in the expression of epithelial-to-mesenchymal transition (EMT) markers in the xenograft tumors, suggesting that RHPN1-AS1 promotes invasion in BC cells by enhancing EMT. These findings suggest that RHPN1-AS1 is a potential prognostic biomarker and therapeutic target for BC.

摘要

乳腺癌(BC)是女性中常见的诊断出的恶性肿瘤。越来越多的证据表明,长链非编码RNA(lncRNA)RHPN1反义RNA 1(RHPN1-AS1)的错误表达与多种癌症类型的发生发展有关。然而,关于lncRNA RHPN1-AS1在BC病理生物学中的表达模式和功能知之甚少。我们评估了癌症基因组图谱数据集中RHPN1-AS1的表达,并分析了RHPN1-AS1表达与BC患者临床病理特征之间的关联。此外,我们通过定量实时聚合酶链反应和原位杂交比较了BC与乳腺非肿瘤样本中RHPN1-AS1的表达,并在BC组织芯片中评估了RHPN1-AS1的预后价值。我们研究了RHPN1-AS1敲低对BC细胞增殖、迁移和侵袭以及肿瘤生长的影响。使用生物信息学分析来预测RHPN1-AS1在BC中的功能。RHPN1-AS1在BC中表达上调,RHPN1-AS1表达升高与BC患者的不良预后密切相关。此外,单因素和多因素分析均显示,RHPN1-AS1是BC预后的重要独立预测因子。在功能上,RHPN1-AS1沉默减弱了BC细胞的增殖、迁移和侵袭,并减少了异种移植模型中的肿瘤生长。此外,RHPN1-AS1沉默与异种移植肿瘤中上皮-间质转化(EMT)标志物表达的降低有关,这表明RHPN1-AS1通过增强EMT促进BC细胞的侵袭。这些发现表明,RHPN1-AS1是BC潜在的预后生物标志物和治疗靶点。

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