|Name||Mr. Pawlos Tsegay|
|Organization or Institution||Florida International University|
|Topic||Biochemistry / Chem Bio.|
Oxidative DNA damage deregulates the expression of miRNAs that regulate DNA repair.
Pawlos Tsegay1 Zhongliang Jiang2 and Yanhao Lai2 and Yuan Liu1,2
Florida International university
miRNAs are small non-coding RNAs that can bind to mRNAs to promote degradation of mRNAs, thereby causing gene silencing. miRNAs usually bind to the 3'-end of an untranslated region of mRNAs to induce mRNA degradation. Previous studies have shown that the expression of several miRNAs including the ones that regulate DNA repair proteins is deregulated in cancer cells suggesting an association of miRNA of DNA damage repair with cancer development. However, the roles of the deregulation of miRNAs that target DNA repair in causing cancer development remain unknown. Since oxidative DNA damage is involved in development of cancer, we hypothesize that oxidative DNA damage induces deregulation of miRNAs that target DNA repair genes leading to downregulation of DNA repair gene and reducing DNA repair capacity. Using human embryonic kidney 293 (HEK293) cells, we examined the level of miR 499a-5p that targets the DNA base excision repair (BER) core enzyme, DNA polymerase β (Pol β), miR 21-5p that targets the mismatch repair proteins, MSH2 and MSH6 and miR155-5p that targets, the mismatch proteins, MLH1, MSH2 and MSH6 under treatment of chromate an oxidative DNA damaging agent and carcinogen with quantitative real-time PCR. We found that a low concentration of chromate at 10 µM led to an increase of miR-499a-5p, miR21-5p, miR155-5p by 1.5-fold, 2.8-fold, and 2.5-fold, respectively. This indicates that oxidative DNA damage upregulated the miRNAs that may in turn downregulate the level of DNA repair proteins from both BER and mismatch repair pathways. This may further result in the accumulation of DNA damage leading to carcinogenesis.