Functions Of MiR-491-5p In ER?-positive Breast Cancer Cells

Breast cancer is one of the most common cancers with the highest incidence and leading cause of cancer-related death in women worldwide,which is a serious disease to threat lives of women.Estrogen receptor ?(ER?)is overexpressed in about 75% of breast cancers,which plays a critical role in the development of breast cancer through associated with a variety of cofactors.miRNA is a regulation factor of gene expression and plays an important role in the regulation of cell apoptosis,proliferation,growth and development of tumor.It is suggested that miRNAs bind to the 3'UTR region of the target gene mRNA by incomplete or complete complementary base pairing,thereby inhibiting the translation of the target gene mRNA or promoting the degradation of the mRNA.Mutation or aberrant expression of miRNAs are closely related to the occurrence of human cancers and can be used as a biomarker for cancer diagnosis.It has been shown that miR-491-5p plays an important role in cancer metastasis and progression,but its role in the breast tumorigenesis is still elusive.In this study,we demonstrated that the expression of miR-491-5p in ER?-positive breast cancer cell lines was significantly lower than that in ER?-negative breast cancer cell lines by real-time qPCR.In order to detect the effect of miR-491-5p on the proliferation of ER?-positive breast cancer cells and ER?-negative breast cancer cells,we overexpressed miR-491-5p in MCF-7?MDA-MB-231 cells,respectively.Trough cell proliferation assay,we found that overexpression of miR-491-5p significantly inhibited the proliferation of MCF-7,but did not affect the proliferation of MDA-MB-231.Through flow cytometric analysis,we found that the overexpression of miR-491-5p could significantly arrest cell cycle of MCF-7 cells at the G1 phase,but could not influence the apoptosis of them.To explore the target gene of miR-491-5p in breast cancer,we used different miRNA prediction websites and found JMJD2 B was a potential target gene of miR-491-5p.Moreover,we further indicated that miR-491-5p could repress the expression of JMJD2 B via directly binding to 3'UTR of its mRNA through Dual-Luciferase assay and Western blot assay.Our data suggested that the molecular mechanism of miR-491-5p regulating ER?-positive breast cancer cell proliferation may be through inhibiting the expressin of JMJD2 B.This study could provide a new insight for the further investigation of the biological mechanism of miR-491-5p in ER?-positive breast cancer development and also provide a potential strategy for the prevention,diagnosis and treatment of breast cancer in the future.