Long non‐coding RNA ES1 controls the proliferation of breast cancer cells by regulating the Oct4/Sox2/miR‐302 axis

Abstract

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.

The Missing Lnc: The Potential of Targeting Triple-Negative Breast Cancer and Cancer Stem Cells by Inhibiting Long Non-Coding RNAs

“…[82] -C01108) miR-200; Regulates stemness factors SOX2 and OCT4 and their downstream targets, miR-306, miR-106b [81].…”

“…The role of lncRNA ES1 (also called LINC01108 or ENST01108) has been studied in human embryonic stem cells [104]. Knockdown of the lncRNA in TNBC MDA-MD-231 and HER2+ SKBR3 cell lines reduced stemness factors SOX2 and OCT4 and their targets, miR-302 and miR-106b, were downregulated [81]. Further, the upregulation of lncRNA ES1 increased expression of Snail/Zeb1 and miR-106b and suppressed the expression of E-cadherin and miR-200, thereby implicating ES1 as a driver of EMT.…”

Application of the microRNA‐302/367 cluster in cancer therapy

“…The downregulation of miR‐302b by its upstream regulator, MIAT, can also promote BC cell migration . High lncRNA ES1 transcript levels in high‐grade and P53‐mutated BC tissues can lead to miR‐302 upregulation and promote cell proliferation and migration . In specific BC cell lines, some scholars have found that vitamin C can reduce the reprogramming efficiency of the miR‐302/367 cluster by downregulating TET1 gene expression, which reverses the inhibition of cell invasion and proliferation by this cluster .…”

“…Similarly, the EC‐specific miR‐302c inhibits HCC growth and angiogenesis by regulating EndMT through MTDH . The upregulation of miR‐302 by lncRNA ES1 promotes EMT in BC cells . Jhdm1a/1b, a vitamin C‐dependent H3K36 demethylase, can cooperate with Oct4 to activate the miR‐302/367 cluster, leading to cell reprogramming .…”

Non-Coding RNAs as Regulators and Markers for Targeting of Breast Cancer and Cancer Stem Cells

“…In addition to these, various lncRNAs such as LUCAT1, lncRNA-Hh, FGF13-AS1, lncRNA ES1 NEAT1 have been reported to be commonly involved in up-regulation of signaling pathways and modulation of stem cell factors (Wnt/β-catenin, Hedgehog, myc, SOX2, OCT4, KLF4, and NANOG). Their role in the promotion of stemness in BC cells and subsequent tumor progression, invasion and metastasis is critical for tumor maintenance and therapeutics [223][224][225][226][227].…”