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miR‐142‐3p is a tumor suppressor that inhibits estrogen receptor expression in ER‐positive breast cancer
Author(s) -
Mansoori Behzad,
Mohammadi Ali,
Gjerstorff Morten F.,
Shirjang Solmaz,
Asadzadeh Zahra,
Khaze Vahid,
Holmskov Uffe,
Kazemi Tohid,
Duijf Pascal H. G.,
Baradaran Behzad
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.28263
Subject(s) - estrogen receptor , microrna , cancer research , carcinogenesis , estrogen receptor alpha , breast cancer , biology , viability assay , cell growth , western blot , apoptosis , cancer , cell cycle , gene , genetics
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.