Role of the histone demethylases KDM5 in breast cancer and melanoma
Histone demethylases (HDMs) have a prominent role in epigenetic regulation and are emerging as potential
therapeutic cancer targets. In particular, HDMs of class 5 (KDM5) ,also known as JARID, are over-expressed in different types of cancers and have a prominent role in cancer cells proliferation and DNA damage repair. In particular, KDM5b (JARID 1B) is upregulated in 90% of human breast cancers and in aggressive forms of melanoma. In order to understand its role in cancer cells physiology, we propose:
a - To use different chemical inhibitors of KDM5 catalytic activity and to test their effects on transcriptome, cell survival and DNA damage repair in breast cancer derived cell lines.
b - To study the functional effects of two different miRNAs which, as we previously showed, target JARID 1B mRNA and significantly modulate its abundance in breast cancer cells.
c - To extend these analyses to melanoma cell lines which over-express JARID1B.