BROWSE

Related Researcher

Author's Photo

Cho, Seung Woo
Research Interests

ITEM VIEW & DOWNLOAD

Promoter of lncRNA Gene PVT1 Is a Tumor-Suppressor DNA Boundary Element

Cited 0 times inthomson ciCited 0 times inthomson ci
Title
Promoter of lncRNA Gene PVT1 Is a Tumor-Suppressor DNA Boundary Element
Author
Cho, Seung WooXu, JinSun, RupingMumbach, Maxwell R.Carter, Ava C.Chen, Y. GraceYost, Kathryn E.Kim, JeewonHe, JingNevins, Stephanie A.Chin, Suet-FeungCaldas, CarlosLiu, S. JohnHorlbeck, Max A.Lim, Daniel A.Weissman, Jpnathan S.Curtis, ChristinaChang, Howard Y.
Issue Date
2018-05
Publisher
CELL PRESS
Citation
CELL, v.173, no.6, pp.1398 - 1412
Abstract
Noncoding mutations in cancer genomes are frequent but challenging to interpret. PVT1 encodes an oncogenic lncRNA, but recurrent translocations and deletions in human cancers suggest alternative mechanisms. Here, we show that the PVT1 promoter has a tumor-suppressor function that is independent of PVT1 lncRNA. CRISPR interference of PVT1 promoter enhances breast cancer cell competition and growth in vivo. The promoters of the PVT1 and the MYC oncogenes, located 55 kb apart on chromosome 8q24, compete for engagement with four intragenic enhancers in the PVT1 locus, thereby allowing the PVT1 promoter to regulate pause release of MYC transcription. PVT1 undergoes developmentally regulated monoallelic expression, and the PVT1 promoter inhibits MYC expression only from the same chromosome via promoter competition. Cancer genome sequencing identifies recurrent mutations encompassing the human PVT1 promoter, and genome editing verified that PVT1 promoter mutation promotes cancer cell growth. These results highlight regulatory sequences of lncRNA genes as potential disease-associated DNA elements. Recurrent mutations in human cancer are found encompassing the promotor for the lncRNA gene PVT1, which regulates MYC transcription via promoter competition for a shared set of enhancers.
URI
https://scholarworks.unist.ac.kr/handle/201301/25759
URL
https://www.sciencedirect.com/science/article/pii/S0092867418304008?via%3Dihub
DOI
10.1016/j.cell.2018.03.068
ISSN
0092-8674
Appears in Collections:
BME_Journal Papers
Files in This Item:
There are no files associated with this item.

find_unist can give you direct access to the published full text of this article. (UNISTARs only)

Show full item record

qrcode

  • mendeley

    citeulike

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

MENU