Event Title

NUCLEOTIDE EXCISION REPAIR REGULATION MAY BE MEDIATED BY MIRNAS IN BREAST CANCER

Location

Atrium

Start Date

14-2-2014 12:00 AM

Description

Objective. The overall objective of the study is to determine the mechanism of reduced DNA repair in early stage sporadic breast cancer. We are focused on finding potential microRNAs (miRs) that regulate nucleotide excision repair (NER) in breast cancer. Background. We have shown that sporadic stage I breast tumors exhibit deficient NER capacity relative to normal breast tissue explants. Five established, stage IV commercially available breast tumor cell lines; MDAMB-231, MCF-7, BT-20, Cama-1, and SK-BR-3, had significantly higher NER capacity compared with 17 early stage tumors. We hypothesize that the molecular mechanisms by which NER is regulated, is through miRs, a regulatory class of small noncoding RNAs that govern gene expression. Methods. Using MiRWalk, we found candidate miRs capable of binding to the 20 canonical NER genes. We performed Nanostring profiling for 4 established cell lines; MDA-MB-231, MCF-7, BT-20, and SK-BR-3, and 2 early stage breast cancer cell lines (JL BTL-10, JL BTL-29). We will transfect specific miRs into our cell lines to determine whether functional repair and gene expression are altered in a predictable way. Results. Using miRWalk, we found that miR-145 significantly binds to 4 out of the 20 canonical genes; RPAp14 (p=0.045), hHRAD23B (p=0.0024), CSB (p=0.0006), TFIIHp52 (p=0.0347). Moreover, down-regulation of miR-145 was statistically significant in 2 early stage cell lines compared to the 4 established cell lines (p= 0.035). Conclusion. MiR-145 is a promising miR by which NER may be regulated. Grants. PFRDG, Florida Breast Cancer Foundation, NIH/NCI and Department of Defense CDMRP

This document is currently not available here.

Share

COinS
 
Feb 14th, 12:00 AM

NUCLEOTIDE EXCISION REPAIR REGULATION MAY BE MEDIATED BY MIRNAS IN BREAST CANCER

Atrium

Objective. The overall objective of the study is to determine the mechanism of reduced DNA repair in early stage sporadic breast cancer. We are focused on finding potential microRNAs (miRs) that regulate nucleotide excision repair (NER) in breast cancer. Background. We have shown that sporadic stage I breast tumors exhibit deficient NER capacity relative to normal breast tissue explants. Five established, stage IV commercially available breast tumor cell lines; MDAMB-231, MCF-7, BT-20, Cama-1, and SK-BR-3, had significantly higher NER capacity compared with 17 early stage tumors. We hypothesize that the molecular mechanisms by which NER is regulated, is through miRs, a regulatory class of small noncoding RNAs that govern gene expression. Methods. Using MiRWalk, we found candidate miRs capable of binding to the 20 canonical NER genes. We performed Nanostring profiling for 4 established cell lines; MDA-MB-231, MCF-7, BT-20, and SK-BR-3, and 2 early stage breast cancer cell lines (JL BTL-10, JL BTL-29). We will transfect specific miRs into our cell lines to determine whether functional repair and gene expression are altered in a predictable way. Results. Using miRWalk, we found that miR-145 significantly binds to 4 out of the 20 canonical genes; RPAp14 (p=0.045), hHRAD23B (p=0.0024), CSB (p=0.0006), TFIIHp52 (p=0.0347). Moreover, down-regulation of miR-145 was statistically significant in 2 early stage cell lines compared to the 4 established cell lines (p= 0.035). Conclusion. MiR-145 is a promising miR by which NER may be regulated. Grants. PFRDG, Florida Breast Cancer Foundation, NIH/NCI and Department of Defense CDMRP