17β-Estradiol up-regulates miR-155 expression and reduces TP53INP1 expression in MCF-7 breast cancer cells

Abstract

In estrogen responsive breast cancer cells, estradiol (E2) is a key regulator of cell proliferation and survival. MiR-155 has emerged as an "oncomiR", which is the most significantly up-regulated miRNA in breast cancer. Moreover, miR-155 is higher in ERα (+) breast tumors than ERα (-), but no one has examined whether E2 regulates miR-155 expression in MCF-7 cells. In this study, the aim was to explore whether miR-155 involved in E2 regulated expression of estrogen responsive genes. We evaluated miR-155 expression in human breast cancer cells by real-time PCR, finding out miR-155 was overexpressed in MCF-7 cells compared with MDA-MB-231 cells. Treatment with E2 in MCF-7 cells increased miR-155 expression, promoting proliferation and decreasing apoptosis, similarly, transfection of miR-155m to MCF-7 cells gave the similar results. In contrast, inhibited miR-155 expression by transfection with miR-155 inhibitors reduced proliferation and promoted apoptosis of MCF-7 cells. Moreover, TP53INP1 is one of the targets of miR-155. E2 negatively regulated TP53INP1 mRNA expression and the protein expression of TP53INP1, cleaved-caspase-3, -8, -9, and p21, whereas transfection with miR-155 inhibitors increased TP53INP1, cleaved-caspase-3, -8, -9, and p21 protein level. These results demonstrated that E2 promoted breast cancer development and progression possibly through increasing the expression of miR-155, which was overexpressed in MCF-7 cells, contributes to proliferation of MCF-7 cells possibly through down-regulating TP53INP1.

miR-155 Drives Metabolic Reprogramming of ER+ Breast Cancer Cells Following Long-Term Estrogen Deprivation and Predicts Clinical Response to Aromatase Inhibitors

“…In particular, miR-155 has been shown to be overexpressed in breast cancers (26)(27)(28) and is modulated by estrogens (29). In addition, miR-155 controls miR-143 expression, a miRNA known to target HK2 in MCF7 cells (30).…”

Garcinol, an Acetyltransferase Inhibitor, Suppresses Proliferation of Breast Cancer Cell Line MCF-7 Promoted by 17β-Estradiol

“…We have accomplished the appropriate concentration of E 2 assay in our previous study (Zhang et al, 2013). The effect of E 2 on promoting proliferation of MCF-7 cells was investigated with CCK-8 assay and the concentration (100 nmol/L) of E 2 in the following experiments was determined according to the rate of proliferation.…”

Unshackling caspase-7 for cancer therapy

“…Except in rare cases, such as MCF-7 cells, in which a 47-base pair deletion in CASP3 has been identified (8), the reason for loss of caspase-3 is generally unknown. Recently, several studies have proposed a direct posttranscriptional regulation of caspase-3 expression by microRNAs (miRNAs) (9)(10)(11). In particular, overexpression of miR-155 has been associated with downregulation of caspase-3 and resistance to apoptosis in the caspase-3-deficient breast cancer cell line MDA-MB-157 (10,11).…”

“…Recently, several studies have proposed a direct posttranscriptional regulation of caspase-3 expression by microRNAs (miRNAs) (9)(10)(11). In particular, overexpression of miR-155 has been associated with downregulation of caspase-3 and resistance to apoptosis in the caspase-3-deficient breast cancer cell line MDA-MB-157 (10,11). In their study, Lin et al demonstrated that upregulation of another miRNA, let-7a-1, decreases caspase-3 expression and is associated with significant accumulation of the XIAP:p19/ p12-CASP7 complex and enhanced chemoresistance (4).…”