Synthetic lethal targeting of superoxide dismutase 1 selectively kills RAD54B-deficient colorectal cancer cells
Authors: Zelda Lichtensztejn
Philip Hieter
Babu V Sajesh
Melanie Bailey
Kirk J McManus
Journal: Genetics (2013)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: RAD54B; colorectal cancer; reactive oxygen species; superoxide dismutase 1; synthetic lethality.
Affiliations: Manitoba Institute of Cell Biology and Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Manitoba, R3E 0V9, Canada., Michael Smith Laboratories, Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, V6T 1Z4, Canada, Manitoba Institute of Cell Biology and Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Manitoba, R3E 0V9, Canada

Abstract:  Synthetic lethality is a rational approach to identify candidate drug targets for selective killing of cancer cells harboring somatic mutations that cause chromosome instability (CIN). To identify a set of the most highly connected synthetic lethal partner genes in yeast for subsequent testing in mammalian cells, we used the entire set of 692 yeast CIN genes to query the genome-wide synthetic lethal datasets. Hierarchical clustering revealed a highly connected set of synthetic lethal partners of yeast genes whose human orthologs are somatically mutated in colorectal cancer. Testing of a small matrix of synthetic lethal gene pairs in mammalian cells suggested that members of a pathway that remove reactive oxygen species that cause DNA damage would be excellent candidates for further testing. We show that the synthetic lethal interaction between budding yeast rad54 and sod1 is conserved within a human colorectal cancer context. Specifically, we demonstrate RAD54B-deficient cells are selectively killed relative to controls via siRNA-based silencing and chemical inhibition and further demonstrate that this interaction is conserved in an unrelated cell type. We further show that the DNA double strand breaks, resulting from increased reactive oxygen species following SOD1 inhibition, persist within the RAD54B-deficient cells and result in apoptosis. Collectively, these data identify SOD1 as a novel candidate cancer drug target and suggest that SOD1 inhibition may have broad-spectrum applicability in a variety of tumor types exhibiting RAD54B deficiencies. 

Retracted: No

PubPeer comments:
 Wearable devices are powerful tools for supporting IoT systems because of their sensing, processing, and communication capability [13,14]. Ref. [13] is as follows: [13] Zhang, L.; Yang, L.; Wang, Z.; Yan, D. Sports Wearable Device Design and Health Data Monitoring Based on Wireless Internet of Things. Microprocess. Microsyst. 2020, 103423, 1u20137. It has been since [withdrawn] . The content of the referenced article is nonsensical and possibly automatically generated, see [this thread] . Did the authors perform at least a cursory check of what they cite? , 
 #1 I want to point out that the review article published by us  Innovative IoT Solutions and Wearable Sensing Systems for Monitoring Human Biophysical Parameters: A Review was submitted on May 4, 2021 (and written in the previous months and weeks). It is obvious that on that date the reference 13 had not yet been withdrawn, otherwise we would not have been able to read and analyze it. Best regards Prof. Paolo Visconti , 
 #2 Dear dr. Visconti, Thank you for your response. I am just curious how it was possible to  read and analyze that article and not notice that it is complete nonsense? ,