An induction of microRNA, miR-7 through estrogen treatment in breast carcinoma

Abstract

BackgroundEstrogen plays an important role in the development of estrogen-dependent breast carcinoma. Recently, several studies demonstrated a possible involvement of several micro RNAs (miRNAs) in the development of resistance to endocrine therapy in breast cancer patients, but the correlation between estrogen actions and miRNA expression in breast carcinoma still remains largely unknown. Therefore, in this study, we examined the in vitro effects of estrogen upon miRNA expression profiles in breast carcinoma.MethodsWe first screened the miRNA expression profiles induced by 17β-Estradiol (E2) using RT2 miRNA PCR Array in the ER-positive breast carcinoma cell line MCF-7. We identified miR-7 as the important miRNA associated with estrogen actions in these cells and further examined the changes of estrogen-dependent EGFR expression by miR-7 in ER-positive or -negative breast carcinoma cell lines including MCF-7. We also evaluated the correlation between miR-7 and EGFR expression in breast carcinoma cells derived from 21 patients using laser capture microdissection combined with quantitative reverse transcriptase-PCR.ResultsSeventeen miRNAs were significantly induced by E2 treatment in the MCF-7 cell line. Among 17 miRNAs induced by estradiol treatment, only miR-7 expression was significantly decreased by subsequent ICI treatment. The expression of miR-7 was up-regulated 2.94-fold by E2 treatment. miR-7 was reported to suppress epidermal growth factor receptor (EGFR) expression in several human malignancies. Transfection of miR-7 significantly suppressed EGFR mRNA levels in MCF-7 cells. Depletion of E2 from cell culture media also increased the expression level of EGFR mRNA in MCF-7 and T-47D cells but not in ER-negative, MDA-MB-231 and SK-BR-3 cells. We also evaluated the status of miR-7 in breast carcinoma tissues, but the correlation between the status of miR-7 and EGFR in carcinoma cells isolated by laser capture microscopy was not detected.ConclusionsThese results suggest that miR-7 may play a role in the development of resistance to endocrine therapy in breast cancer patients through regulating EGFR expression of carcinoma cells.

17β-estradiol ameliorates age-associated loss of fibroblast function by attenuating IFN-γ/STAT1-dependent miR-7 upregulation

“…Furthermore, the combined inhibition of ER and EGFR caused antiproliferative effects in cancer cells (Stabile et al ., 2005). However, in MCF‐7 breast cancer cells, E2 treatments were detrimental to EGFR expression in an ERα‐ and miR‐7‐dependent manner (Masuda et al ., 2012). …”

Role of microRNA-7 in digestive system malignancy

“…Also, miR-7 is expressed abundantly in human pancreas and endocrine cells and has a specific role in endocrine cell differentiation and function [10] . It has been demonstrated that miR-7 is a tumor suppressor in breast, lung and ovarian cancers, and glioblastoma, mainly focusing on its relationship with EGFR [11][12][13][14][15] . Accumulating evidence shows that miR-7 can simultaneously target a variety of mRNAs involved in diverse signaling pathways in different tumors.…”

Long-term exposure of MCF-7 breast cancer cells to ethanol stimulates oncogenic features

“…In some cases, ethanol induced upregulation is also seen after estrogen treatment, such as in miR-27a and b (96). The fact that ethanol affected any particular miR in this study did not necessarily coincide with affects on other miRs that would be expected to change comcomitantly if ethanol action were limited to one specific pathway such as the estrogenic pathway: thus upregulated miRs such as miR-107, miR-424, miR-570, miR-618, and miR-760 (95), miR-21 (28), miR-34b (97), miR-98 (98), miR-19A and miR-24 (96), miR-26a and b (99), miR-17 (100,101), miR-7 (102), or miR-190a (103); or downregulated miRs such as miR-16, miR-143, or miR-203 (104). Interestingly, the latter is the opposite of what we observed with ethanol.…”