Adjacent long non-coding RNA PVT1 and MYC co-operate in breast cancer with gain of 8q24

Abstract

Copy number gain of 8q24 is a common structural abnormality in human cancers. Although <italic>MYC</italic> is usually assumed to be responsible for 8q24 gain cancer, the role of the other genes in the 8q24 region remains mostly unknown. We derived chromosome engineered mice with an extra copy of <italic>Myc-Gsdmc</italic> region which is syntenic to the common region gained in human 8q24-associated cancer. These mice show aberrant differentiation and loss of proliferation arrest of mammary epithelial cells, excessive branching of mammary ducts, and increased sensitization to mammary tumors. In contrast, mice carrying a duplication of either <italic>Myc</italic> or <italic>Pvt1-Gsdmc</italic> were found to be insufficient for neoplasia. We show that the long non-coding RNA Pvt1 and adjacent <italic>Myc</italic> can co-operate in tumorigenesis. Furthermore, PVT1 can regulate MYC protein stability in human breast cancer cells. Our study reveals a novel mechanism of MYC regulation by a long non-coding RNA in cancer cells and could provide therapeutic targets.