当前位置: X-MOL 学术npj Breast Cancer › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
LncRNA RP11-19E11 is an E2F1 target required for proliferation and survival of basal breast cancer.
npj Breast Cancer ( IF 6.5 ) Pub Date : 2020-01-06 , DOI: 10.1038/s41523-019-0144-4
A Giro-Perafita 1 , L Luo 1 , A Khodadadi-Jamayran 2 , M Thompson 1 , B Akgol Oksuz 2, 3 , A Tsirigos 2, 4 , B D Dynlacht 4 , I Sánchez 4 , F J Esteva 1
Affiliation  

Long non-coding RNAs (lncRNAs) play key roles in the regulation of breast cancer initiation and progression. LncRNAs are differentially expressed in breast cancer subtypes. Basal-like breast cancers are generally poorly differentiated tumors, are enriched in embryonic stem cell signatures, lack expression of estrogen receptor, progesterone receptor, and HER2 (triple-negative breast cancer), and show activation of proliferation-associated factors. We hypothesized that lncRNAs are key regulators of basal breast cancers. Using The Cancer Genome Atlas, we identified lncRNAs that are overexpressed in basal tumors compared to other breast cancer subtypes and expressed in at least 10% of patients. Remarkably, we identified lncRNAs whose expression correlated with patient prognosis. We then evaluated the function of a subset of lncRNA candidates in the oncogenic process in vitro. Here, we report the identification and characterization of the chromatin-associated lncRNA, RP11-19E11.1, which is upregulated in 40% of basal primary breast cancers. Gene set enrichment analysis in primary tumors and in cell lines uncovered a correlation between RP11-19E11.1 expression level and the E2F oncogenic pathway. We show that this lncRNA is chromatin-associated and an E2F1 target, and its expression is necessary for cancer cell proliferation and survival. Finally, we used lncRNA expression levels as a tool for drug discovery in vitro, identifying protein kinase C (PKC) as a potential therapeutic target for a subset of basal-like breast cancers. Our findings suggest that lncRNA overexpression is clinically relevant. Understanding deregulated lncRNA expression in basal-like breast cancer may lead to potential prognostic and therapeutic applications.

中文翻译:

LncRNA RP11-19E11 是基底乳腺癌增殖和存活所需的 E2F1 靶标。

长链非编码RNA (lncRNA) 在调节乳腺癌的发生和进展中发挥着关键作用。LncRNA 在乳腺癌亚型中表达存在差异。基底样乳腺癌通常是低分化肿瘤,富含胚胎干细胞特征,缺乏雌激素受体、孕激素受体和 HER2(三阴性乳腺癌)的表达,并显示增殖相关因子的激活。我们假设 lncRNA 是基底乳腺癌的关键调节因子。使用癌症基因组图谱,我们发现与其他乳腺癌亚型相比,lncRNA 在基底肿瘤中过度表达,并且在至少 10% 的患者中表达。值得注意的是,我们鉴定出了表达与患者预后相关的 lncRNA。然后,我们评估了候选 lncRNA 子集在体外致癌过程中的功能。在此,我们报告了染色质相关 lncRNA RP11-19E11.1 的鉴定和表征,该 RNA 在 40% 的基底原发性乳腺癌中表达上调。原发性肿瘤和细胞系中的基因集富集分析揭示了 RP11-19E11.1 表达水平与 E2F 致癌途径之间的相关性。我们证明这种 lncRNA 与染色质相关,并且是 E2F1 靶标,其表达对于癌细胞增殖和存活是必需的。最后,我们使用 lncRNA 表达水平作为体外药物发现的工具,将蛋白激酶 C (PKC) 确定为基底样乳腺癌子集的潜在治疗靶点。我们的研究结果表明 lncRNA 过度表达具有临床相关性。
更新日期:2020-01-06
down
wechat
bug