Keshavarz Mostafa, Asadi Malek Hossein, Riahi-Madvar Ali
Department of Biotechnology, Institute of Science and High Technology and Environmental Sciences, Graduate University of Advanced Technology, Kerman, Iran.
J Cell Biochem. 2019 Oct;120(10):18398-18405. doi: 10.1002/jcb.29152. Epub 2019 Jun 18.
Breast cancer is the second most common cancer and estimates to be responsible for 20% of all cancer patients. Breast cancer has several subtypes including luminal A, luminal B, normal breast-like, basal-like, and human epidermal growth factor receptor 2 (HER2)-enriched. HER2-positive breast cancer cells have higher HER2 expression than other breast cancer subtypes. This subtype is the most aggressive breast cancer subtype and has more ability to metastasis than other breast cancer subtypes. HER2 is a growth-promoting protein that is overexpressed in approximately 20 to 30% of breast cancers and its overexpression is strongly related to poor prognosis. New studies suggested that HER2 expression is correlated with cancer stem cell (CSC) markers in breast cancer. ES3 transcript as a pluripotency long noncoding RNA (lncRNA) is linked to pluripotency transcriptional networks in human embryonic stem cells, but its function in breast cancer is not clarified. In the current research, we found ES3 upregulation in breast cancer and its diagnostic value in breast cancer diagnosis. Furthermore, our findings revealed that ES3 transcript has a high expression in high-grade and high-stage breast tumors. In addition, our data demonstrated that ES3 expression downregulated during neural differentiation. Therefore, its expression may be correlated to breast tumor differentiation status. Notably, a high expression level of ES3 in HER2-positive breast tumor tissues motivated us to investigate the effect of HER2 on ES3 expression by blocking HER2 activity with lapatinib. The results showed that ES3 expression suppressed when HER2 activity was blocked. In summary, for the first time, we found that lncRNA ES3 was significantly upregulated in HER2-positive breast tumors and may contribute to breast cancer proliferation as a downstream target of HER2.
乳腺癌是第二常见的癌症，估计占所有癌症患者的20%。乳腺癌有几种亚型，包括腔面A型、腔面B型、正常乳腺样型、基底样型和人表皮生长因子受体2（HER2）富集型。HER2阳性乳腺癌细胞的HER2表达高于其他乳腺癌亚型。这种亚型是最具侵袭性的乳腺癌亚型，比其他乳腺癌亚型更易发生转移。HER2是一种促进生长的蛋白质，在大约20%至30%的乳腺癌中过度表达，其过度表达与预后不良密切相关。新的研究表明，HER2表达与乳腺癌中的癌症干细胞（CSC）标志物相关。ES3转录本作为一种多能性长链非编码RNA（lncRNA）与人类胚胎干细胞中的多能性转录网络相关，但它在乳腺癌中的功能尚不清楚。在当前的研究中，我们发现ES3在乳腺癌中上调及其在乳腺癌诊断中的价值。此外，我们的研究结果显示ES3转录本在高级别和高分期乳腺肿瘤中高表达。此外，我们的数据表明ES3表达在神经分化过程中下调。因此，其表达可能与乳腺肿瘤分化状态相关。值得注意的是，ES3在HER2阳性乳腺肿瘤组织中的高表达促使我们通过用拉帕替尼阻断HER2活性来研究HER2对ES3表达的影响。结果表明，当HER2活性被阻断时，ES3表达受到抑制。总之，我们首次发现lncRNA ES3在HER2阳性乳腺肿瘤中显著上调，并可能作为HER2的下游靶点促进乳腺癌增殖。
