Upregulation of pluripotent long noncoding RNA ES3 in HER2-positive breast cancer.

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.

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