ERβ regulates miR-21 expression and inhibits invasion and metastasis in cancer cells

In human, estrogens play important roles in many physiological processes, and is also found to be connected with numerous cancers. In these diseases, estrogen mediates its effects through the estrogen receptor (ER), which serves as the basis for many current clinical diagnosis. Two forms of the estrogen receptor have been identified, ER alpha and ER beta, and show different and specific functions. The two estrogen receptors belong to a family of ligand-regulated transcription factors. Estrogen via ER alpha stimulates proliferation in the breast, uterus, and developing prostate, while estrogen via ER beta inhibits proliferation and promotes differentiation in the prostate, mammary gland, colon, lung, and bone marrow stem cells. MicroRNAs (miRs) are small non-coding RNA molecules that occur naturally and downregulate protein expression by translational blockade of the target mRNA or by promoting mRNA decay. MiR-21 is one of the most studied miRNAs in cancers. MiR-21 is overexpressed in the most solid tumors, promoting progression and metastasis. The miR-21 gene is located on the chromosome 17, in the 10th intron of a protein-coding gene, TMEM49. While, the function of TMEM49 is currently unknown. Our experiment is designed to identity the relationship between miR-21 and ER beta in cancer progression. The human cancer cells were transfected with ER beta. Real-time PCR analysis showed that the expression level of miR-21 was significantly inhibited down by ER beta treatment. As MTT assay showed the tumor cell survival rate was also inhibited significantly. G(0)/G(1) phase cell cycle arrest was founded and tumor cell apoptosis was induced in ER beta group.