Pericentromeric Satellite III transcripts induce etoposide resistance

Kanne J, Hussong M, Isensee J, Munoz-Lopez A, Wolffgramm J, Hess F, Grimm C, Bessonov S, Meder L, Wang J, Reinhardt HC, Odenthal M, Hucho T, Buettner R, Summerer D, Schweiger MR (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Cell Death & Disease Nature Publishing Group: Open Access Journals - Option B / Nature Publishing Group

Book Volume: 12

Article Number: 530

Journal Issue: 6

DOI: 10.1038/s41419-021-03810-9

Abstract

Non-coding RNA from pericentromeric satellite repeats are involved in stress-dependent splicing processes, maintenance of heterochromatin, and are required to protect genome stability. Here we show that the long non-coding satellite III RNA (SatIII) generates resistance against the topoisomerase IIa (TOP2A) inhibitor etoposide in lung cancer. Because heat shock conditions (HS) protect cells against the toxicity of etoposide, and SatIII is significantly induced under HS, we hypothesized that the protective effect could be traced back to SatIII. Using genome methylation profiles of patient-derived xenograft mouse models we show that the epigenetic modification of the SatIII DNA locus and the resulting SatIII expression predict chemotherapy resistance. In response to stress, SatIII recruits TOP2A to nuclear stress bodies, which protects TOP2A from a complex formation with etoposide and results in decreased DNA damage after treatment. We show that BRD4 inhibitors reduce the expression of SatIII, restoring etoposide sensitivity.

Authors with CRIS profile

Lydia Meder

Involved external institutions

Universität zu Köln DE Germany (DE) Technische Universität Dortmund DE Germany (DE) Universität Duisburg-Essen (UDE) DE Germany (DE) Universitätsklinikum Köln DE Germany (DE)

How to cite

APA:

Kanne, J., Hussong, M., Isensee, J., Munoz-Lopez, A., Wolffgramm, J., Hess, F.,... Schweiger, M.R. (2021). Pericentromeric Satellite III transcripts induce etoposide resistance. Cell Death & Disease, 12(6). https://doi.org/10.1038/s41419-021-03810-9

MLA:

Kanne, Julian, et al. "Pericentromeric Satellite III transcripts induce etoposide resistance." Cell Death & Disease 12.6 (2021).

BibTeX: Download