Effects on prostate cancer cells of targeting RNA polymerase III

Nucleic Acids Research
John L PetrieRobert J White

Abstract

RNA polymerase (pol) III occurs in two forms, containing either the POLR3G subunit or the related paralogue POLR3GL. Whereas POLR3GL is ubiquitous, POLR3G is enriched in undifferentiated cells. Depletion of POLR3G selectively triggers proliferative arrest and differentiation of prostate cancer cells, responses not elicited when POLR3GL is depleted. A small molecule pol III inhibitor can cause POLR3G depletion, induce similar differentiation and suppress proliferation and viability of cancer cells. This response involves control of the fate-determining factor NANOG by small RNAs derived from Alu short interspersed nuclear elements. Tumour initiating activity in vivo can be reduced by transient exposure to the pol III inhibitor. Untransformed prostate cells appear less sensitive than cancer cells to pol III depletion or inhibition, raising the possibility of a therapeutic window.

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Citations

Sep 22, 2019·International Journal of Molecular Sciences·András PenyigeBálint Nagy
Feb 10, 2021·Nature Structural & Molecular Biology·Mathias GirbigChristoph W Müller
Aug 17, 2021·Frontiers in Molecular Biosciences·Elisabeth LataMartin Teichmann

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Methods Mentioned

BETA
xenograft
PCR
Protein Assay
Immunoprecipitation
ChIP
xenografts
transfection
co-immunoprecipitation
biopsies
ChIP-Seq

Software Mentioned

ImageJ
Experiment Manager
Zen
ELDA
Summit
DICER

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