Oncofetal protein LIN28B may be a synthetic lethal drug target in a subset of pancreatic cancers

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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 [1]. Roughly 20% of the pancreatic cancer cell lines in the cancer cell line encyclopedia (CCLE) express LIN28B (Figure 1).

 

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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 [2]. They may well have similar effects on LIN28B+ pancreatic cancer cells, which will be important to investigate.

 

Refs

  1. 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.
  2. 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.
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