The Correlation Study Of PHCDH Regulation By MiRNAs In ER-negative Breast Cancer

BackgroundsBreast cancer is a common malignancy mainly affecting the female. The fatality rate is high. Breast cancer has become a serious threat to China’s female life. In recent years, due to the good availability of early screening and breakthroughs of anti-cancer therapies, the survival ratio of breast cancer has been inereasing. But the detailed and diversified mechanism still remains further investigation. With the molecular biology advancing, targeted therapies get more and more attentions. Hence, it’s of great importance to search relevant genes which play significant roles in regulation of breast cancer. Phosphoglycerate dehydrogenase (PHGDH) is the enzyme in the pathway of serine synthesis. It recently has been found that PHGDH gene is amplified and that PHGDH is over-expressed. Moreover. breast cancer cells needs PHGDH to remain survival and proliferation. MicroRNAs is a type of non-coding RNA composed of 21-22nt. microRNAs can regulategene expression while not in a way of complete inhibition. Studies have well established the roles of microRNAs in many significant cellular and molecular events, such as development, dif-ferentiation, proliferation, oncogenesis, metabolism and disease advancement. In rec-ently years, results show that microRNAs play a role in tumor as well. And micro RNA genes could be tumor suppressor genes as well as oncogenes. Such variaty of functions make microRNAs be a hotspot in the field of gene regulation research.This project focuses on PHGDH as our target gene. We predict possible microRNAs which target 3’UTR of our target gene. i.e. PHGDH. We choose 6 possible microRNAs to do further investigation and verify whether one or more of them target PHGDH and thus play a role in the tumorigenesis of breast cancer. We shall finally analyze the possibility to develop a cure for refractory breast cancer.ObjectiveThis study was to explore the target genes PHGDH miRNA molecular regulation mechanism in estrogen receptor negative breast cancer, analysis role by miRNA regulation PHGDH in breast cancer cells and the feasibility of the treatment.MethodsWe predict possible microRNAs which target 3’UTR of our target gene, i.e. PHGDH, by using TargetScan, MiRanda and PicTar. We choose 6 possible microRNAs to do further investigation. We cultured MCF-7, T47D, ZR-75-1 and MDA-MB-231 cells and examined PHGDH mRNA level in these cells with qRT-PCR. We over expressed miRNA mimics in MDA-MB-231 cells and examined the apoptosis and proliferation status by using CCK-8.ResultsResults from bioinformatic sofewares show that six miRNAs could regulate PHGDH expression, which are miR-27, miR-28.miR-137, miR-759, miR-1290 and miR-4718. Results of qRT-PCR show that miR-128 is negatively associated with PHGDH mRNA level. By over expressing miR-128 mimic, the PHGDH expression is down regulated. And with co-treatment of ER-TAM. up-regulation of miR-128 could inhibit the proliferation of MDA-MB-231.ConclusionsMiR-128 regulates gene expression of PHGDH. There is a possibility that we can develop a novel medicine that targets mir-128 to treat ER-negative breast cancer.