Estrogen receptor coactivator Mediator Subunit 1(MED1) as a tissue-specific therapeutic target in breast cancer

Breast cancer,one of the most frequent cancer types,is a leading cause of death in women worldwide.Estrogen receptor(ER)αis a nuclear hormone receptor that plays key roles in mammary gland development and breast cancer.About 75%of breast cancer cases are diagnosed as ER-positive;however,nearly half of these cancers are either intrinsically or inherently resistant to the current anti-estrogen therapies.Recent studies have identified an ER coactivator,Mediator Subunit 1(MED1),as a unique,tissue-specific cofactor that mediates breast cancer metastasis and treatment resistance.MED1 is overexpressed in over 50%of human breast cancer cases and co-amplifies with another important breast cancer gene,receptor tyrosine kinase HER2.Clinically,MED1 expression highly correlates with poor disease-free survival of breast cancer patients,and recent studies have reported an increased frequency of MED1 mutations in the circulating tumor cells of patients after treatment.In this review,we discuss the biochemical characterization of MED1 and its associated MED1/Mediator complex,its crosstalk with HER2 in anti-estrogen resistance,breast cancer stem cell formation,and metastasis both in vitro and in vivo.Furthermore,we elaborate on the current advancements in targeting MED1 using state-of-the-art RNA nanotechnology and discuss the future perspectives as well.

Mutation of MED12 is not a frequent occurrence in prostate cancer of Korean patients

Prostate cancer is one of the major health care problems, but the molecular pathogenesis has been relatively insufficiently elucidated. Recently, whole exome sequencing of prostate cancer identified recurrent mutations involving MED12 in Caucasian patients, which finding was not reproduced in one subsequent study by Sanger sequencing. Thus, we investigated mutation status of MED12 in exons 2 and 26 by Sanger sequencing in 102 radical prostatectomy cases from Korean patients. The analysis found the mutation in none of the cases. Therefore, MED12 mutation does not appear to represent a significant molecular alteration in this cohort of patients according to the analysis by the traditional ＂gold standard.＂

Hsa-miR-637 inhibits human hepatocyte proliferation by targeting Med1-interacting proteins

Background:Recent studies have shown that mediator complex subunit 1(Med1)can significantly affect hepatocyte proliferation and differentiation.Acting as a tumor suppressor,microRNA-637(hsa-miR-637)can inhibit the growth of hepatocarcinoma cells and further induce cell apoptosis.However,the function of hsa-miR-637 and its target genes during liver regeneration remains to be elucidated.Methods:This study used co-immunoprecipitation(Co-IP)assay,transfection,luciferase reporter assay,functional assay by cell counting kit-8(CCK-8),Annexin V-FITC/propidium iodide apoptosis assay,and quantitative polymerase chain reaction analysis of chromatin immunoprecipitation(ChIP)for analysis.Results:Hsa-miR-637 has been suggested to suppress the expression of two Med1-interacting nuclear receptors,identified as the peroxisome proliferator-activated receptor alpha(PPARA)and thyroid hormone receptor alpha(THRA)at the transcriptional and translational levels in the human liver HL-7702 cell line.The interaction between Med1 and PPARA/THRA in HL-7702 cells was then confirmed.The transcriptional repression of hsa-miR-637 on PPARA and THRA was also demonstrated.Moreover,hsamiR-637 has been determined to suppress the proliferation of HL-7702 cells.Furthermore,cell cycle arrest of HL-7702 cells was induced by transfection of hsa-miR-637 at the S phase,but its apoptosis failed.Finally,PPARA was indicated to directly bind to the promoter of some transcription factors,like bcatenin,mouse double minute 2(MDM2),and p53.Conclusions:This study has confirmed that hsa-miR-637 plays an antiproliferative role during liver regeneration,which may contribute in understanding the regenerative process of the liver.