Targeting Mutant Dicer Tumorigenesis in Pleuropulmonary Blastoma via Inhibition of RNA Polymerase I

DICER1 mutations predispose to increased risk for various cancers, particularly pleuropulmonary blastoma (PPB), the commonest lung malignancy of childhood. There is a paucity of directly actionable molecular targets as these tumors are driven by loss-of-function mutations of DICER1. Therapeutic development for PPB is further limited by a lack of biologically and physiologically-representative disease models. Given recent evidence of Dicer's role as a haploinsufficient tumor suppressor regulating RNA polymerase I (Pol I), Pol I inhibition could abrogate mutant Dicer-mediated accumulation of stalled polymerases to trigger apoptosis.

Source: Translational Research - March 13, 2023 Category: Research Authors: Megan Rui En Wong, Kia Hui Lim, Esther Xuan Yi Hee, Huiyi Chen, Chik Hong Kuick, Aw Sze Jet, Kenneth Tou En Chang, Nurfarhanah Syed Sulaiman, Sharon YY Low, Septian Hartono, Anh Nguyen Tuan Tran, Summaiyya Hanum Ahamed, Ching Mei Joyce Lam, Shui Yen Soh, Source Type: research