ES1 is a long non‐coding RNA (lncRNA) that regulates pluripotency of human embryonic stem cells, which is known to be a downstream target of stemness factors Oct4 and Nanog, and serves as a modular scaffold for Sox2. However, the role of ES1 in cancer biology is not fully characterized. The results of our study show that ES1 transcript is upregulated in both high‐grade and P53‐mutated breast tumor tissues. Knockdown experiments show that ES1 suppression in breast cancer cells restricts cancer cell proliferation and cell cycle progression. Moreover, ES1 inhibition can also induce apoptosis and cellular senescence. Additionally, our data reveal that ES1 transcript promotes cell migration as well as the epithelial to mesenchymal transition of breast cancer cells. Furthermore, loss of ES1 expression downregulates the expression of Oct4/Sox2 and consequently leads to downregulation of their targets, miR‐302 and miR‐106b. Altogether, for the first time, our findings reveal that ES1 controls the proliferation and death of breast cancer cells by regulating the Oct4/Sox2/miR‐302/miR‐106b axis.

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.

Long non-coding RNAs (lncRNAs) are known to be important regulators in different cellular processes and are implicated in various human diseases. Recently, lncRNA PNKY has been found to be involved in pluripotency and differentiation of embryonic and postnatal neural stem cells (NSCs); however, its expression and function in cancer cells is still unclear. In the present study, we observed the expression of PNKY in various cancer tissues, including brain, breast, colorectal, and prostate cancers. In particular, we demonstrated that lncRNA PNKY was significantly upregulated in breast tumors, especially high-grade tumors. Knock down experiments indicated that the suppression of PNKY in breast cancer cells could restrict their proliferation by promoting apoptosis, senescence, and cell cycle disruption. Moreover, the results demonstrated that PNKY may play a crucial role in the cell migration of breast cancer cells. We further found that PNKY may trigger EMT in breast cancer cells by upregulating miR-150 and restricting the expression of Zeb1 and Snail. This study is the first to provide new evidence on the expression and biological function of PNKY in cancer cells and its potential contribution to tumor growth and metastasis.

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