Background/Objectives: Long noncoding RNAs (lncRNAs) are known to play key roles in breast cancers; however, detailed mechanistic studies of lncRNA function have not been conducted in large cohorts of breast cancer tumors, nor has inter-donor and inter-subtype variability been taken into consideration for these analyses. Here we provide the first identification and annotation of the human BORG lncRNA gene. Methods/Results: Using multiple tumor cohorts of human breast cancers, we show that while BORG expression is strongly induced in breast tumors as compared to normal breast tissues, the extent of BORG induction varies widely between breast cancer subtypes and even between different tumors within the same subtype. Elevated levels of BORG in breast tumors are associated with the acquisition of core cancer aggression pathways, including those associated with basal tumor and pluripotency phenotypes and with epithelial–mesenchymal transition (EMT) programs. While a subset of BORG-associated pathways was present in high BORG-expressing tumors across all breast cancer subtypes, many were specific to tumors categorized as triple-negative breast cancers. Finally, we show that genes induced by heterologous expression of BORG in murine models of TNBC both in vitro and in vivo strongly overlap with those associated with high BORG expression levels in human TNBC tumors. Conclusion: Our findings implicate human BORG as a novel driver of the highly aggressive basal TNBC tumor phenotype.
背景/目的：长链非编码RNA（lncRNA）在乳腺癌中发挥关键作用已得到公认；然而，针对lncRNA功能的详细机制研究尚未在大型乳腺癌肿瘤队列中展开，且现有分析亦未充分考虑供体间及亚型间的异质性。本研究首次对人类BORG lncRNA基因进行了鉴定与功能注释。方法/结果：通过分析多个人类乳腺癌肿瘤队列，我们发现与正常乳腺组织相比，BORG在乳腺肿瘤中表达显著上调，但其诱导程度在不同乳腺癌亚型间甚至同一亚型的不同肿瘤间存在广泛差异。乳腺肿瘤中BORG水平升高与核心癌症侵袭通路的激活相关，包括与基底型肿瘤表型、多能性表型以及上皮-间质转化（EMT）程序相关的通路。虽然部分BORG相关通路在所有乳腺癌亚型的高BORG表达肿瘤中普遍存在，但更多通路特异性存在于三阴性乳腺癌分类的肿瘤中。最后，我们通过小鼠TNBC模型（涵盖体外与体内实验）证明，异源表达BORG所诱导的基因与人类TNBC肿瘤中高BORG表达相关基因存在高度重叠。结论：我们的研究结果表明，人类BORG是驱动高侵袭性基底型三阴性乳腺癌表型的新型关键因子。
Induction of Invasive Basal Phenotype in Triple-Negative Breast Cancers by Long Noncoding RNA BORG
肿瘤(癌症)患者之家