| Estrogen receptors (ERs) are involved in the development of many types of malignant
tumors, in particular, breast cancer. Among others, ERs affect cell growth,
proliferation, and differentiation. The microRNA (miRNA) miR‐142‐3p has been
shown to inhibit carcinogenesis by regulating various cellular processes, including cell
cycle progression, cell migration, apoptosis, and invasion. It does so via targeting
molecules involved in a range of signaling pathways. We surgically collected 20
ER‐positive breast cancer samples, each with matched adjacent normal breast tissue,
and measured the expression of miR‐142‐3p via quantitative real‐time polymerase
chain reaction (qRT‐PCR). Bioinformatics methods, luciferase reporter assay,
qRT‐PCR, and western blot analysis were used to assess whether miR‐142‐3p could
target ESR1, which encodes the estrogen receptor, in ER‐positive breast cancer cells
and patient samples. We also restored miRNA expression and performed cell viability,
cytotoxicity, and colony formation assays. Western blot analysis and qRT‐PCR were
used to study the expression of apoptosis and stemness markers. We found that
miR‐142‐3p is downregulated in ER‐positive breast cancers. Restoration of miR‐142‐
3p expression in ER‐positive breast cancer cells reduced cell viability, induced
apoptosis via the intrinsic pathway and decreased both colony formation and the
expression of stem cell markers. Bioinformatic analysis predicted miR‐142‐3p could
bind to 3′‐untranslated region ESR1 messenger RNA (mRNA). Consistently, we
demonstrated that miR‐142‐3p reduced luciferase activity in ER‐positive breast
cancer cells, and decreased ESR1 expression in both mRNA and protein levels. The
results revealed miR‐142‐3p and ESR1 expression correlated negatively in
ER‐positive breast cancer samples. The results suggest miR‐142‐3p acts as a tumor
suppressor via multiple mechanisms. Thus, restoration of miR‐142‐3p expression, for
example, via miRNA replacement therapy, may represent an effective strategy for the
treatment of ER‐positive breast cancer patients. |