Presentation Abstract

Abstract Number: 4192
Presentation Title: LIN28 mRNA targets in breast cancer cells
Presentation Time: Tuesday, Apr 03, 2012, 1:00 PM - 5:00 PM
Location: McCormick Place West (Hall F), Poster Section 10
Poster Section: 10
Poster Board Number: 8
Author Block: Harriet K. Kinyamu, Jun Yang, Trevor K. Archer. NIEHS, Research Triangle Park, NC
Abstract Body: LIN28 is a RNA binding protein and a pluripotency factor. It represses tumor suppressing microRNA let-7 and activates let-7 oncogene targets such as HMGA2 and c-Myc. Recent reports show that LIN28 overexpression promotes tumor cell migration and cellular transformation through repression of let-7, and that overexpression is associated with advanced stages of disease, including breast cancer. The molecular function and mode of action of LIN28 in breast cancer is not yet elucidated. To further understand the function of LIN28, we explored LIN28 mRNA targets in breast cancer cells using RNA-protein immunoprecipitation (RIP) followed by RNA sequencing (RIP-Seq). Only 418 genes (1.7% of the human total genes) are enriched more than 1.0 RPKM (reads per kilobase of exon model per million mapped reads) in the LIN28 RIP relative to control RIP. LIN28 mRNA targets in breast cancer cells function in processes that drive tumorigenesis, including cell proliferation, inflammation and metastasis. Therapeutic drugs inhibiting LIN28 could be promising in treatment of cancer. Our experiments also demonstrate that MG132, a proteasome inhibitor, inhibits LIN28 expression and modulates expression of LIN28 mRNA targets in breast cancer cells. Studies are ongoing to reveal the mechanisms by which LIN28 regulates bound targets and how proteasome inhibitors impact this regulation.