LIN28B is not normally expressed in the pancreas and it represses the expression of the tumour suppressor let-7 microRNA. Downregulation of the protein deacetylase Sirtuin-6 (SIRT6) may promote LIN28B expression. Pancreatic cancer cell lines that express LIN28B are dependent on the protein for growth . Roughly 20% of the pancreatic cancer cell lines in the cancer cell line encyclopedia (CCLE) express LIN28B (Figure 1).
|Figure 1: Scatter plot of SIRT6 (x-axis) and LIN28B (y-axis) mRNA expression in 44 pancreatic cancer cell lines (data source CCLE). Negative trend line shown. RMA = robust multiarray average (mRNA expression).|
Importantly the bromodomain inhibitor JQ1 and the histone deacetylase inhibitor panobinostat synergistically reduced LIN28B expression in neuroblastoma cells . They may well have similar effects on LIN28B+ pancreatic cancer cells, which will be important to investigate.
- Kugel, Sita, Carlos Sebastián, Julien Fitamant, Kenneth N. Ross, Supriya K. Saha, Esha Jain, Adrianne Gladden, et al. ‘SIRT6 Suppresses Pancreatic Cancer through Control of Lin28b’. Cell 165, no. 6 (2 June 2016): 1401–15. doi:10.1016/j.cell.2016.04.033.
- Shahbazi, Jeyran, Pei Y. Liu, Bernard Atmadibrata, James E. Bradner, Glenn M. Marshall, Richard B. Lock, and Tao Liu. ‘The Bromodomain Inhibitor JQ1 and the Histone Deacetylase Inhibitor Panobinostat Synergistically Reduce N-Myc Expression and Induce Anticancer Effects’. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research 22, no. 10 (15 May 2016): 2534–44. doi:10.1158/1078-0432.CCR-15-1666.