KRCC1: A potential therapeutic target in ovarian cancer

Abstract

Using a systems biology approach to prioritize potential points of intervention in ovarian cancer, we identified the lysine rich coiled‐coil 1 (KRCC1), as a potential target. High‐grade serous ovarian cancer patient tumors and cells express significantly higher levels of KRCC1 which correlates with poor overall survival and chemoresistance. We demonstrate that KRCC1 is predominantly present in the chromatin‐bound nuclear fraction, interacts with HDAC1, HDAC2, and with the serine‐threonine phosphatase PP1CC. Silencing KRCC1 inhibits cellular plasticity, invasive properties, and potentiates apoptosis resulting in reduced tumor growth. These phenotypes are associated with increased acetylation of histones and with increased phosphorylation of H2AX and CHK1, suggesting the modulation of transcription and DNA damage that may be mediated by the action of HDAC and PP1CC, respectively. Hence, we address an urgent need to develop new targets in cancer.

scTenifoldKnk: an efficient virtual knockout tool for gene function predictions via single-cell gene regulatory network perturbation

“…A principal component analysis (PCA) was used to confirm that perturbation profiles of Mta1, Akap7 and Zranb1 differ most from that of Cftr , while the perturbation profiles of Krcc1 and Rps8 are relatively more similar to that of Cftr ( Supplementary Figure S4 ). The two genes closer to Cftr, Krcc1 and Rps8 have been reported to play a role in regulating cellular plasticity and fibrotic process [54, 55]. These results suggest that scTenifoldKnk specifically reveals gene function using the KO gene’s perturbation profile rather than the KO gene’s expression profile.…”

“…Both Krcc1 and Rps8 have been reported to play a role in regulating cellular plasticity and fibrotic process. 35,36 Duchenne muscular dystrophy…”

Characterizing kinase intergenic-breakpoint rearrangements in a large-scale lung cancer population and real-world clinical outcomes

“… 29 Whereas in ovarian cancer, KRCC1 was found to be highly expressed and associated with poor prognosis. 30 We identified one IGR in which the KRCC1 promoter and the RET kinase domain were rearranged together. The third example was a ROS1 IGR where the intact kinase domain of ROS1 was fused to the promoter of MAGI1.…”

scTenifoldKnk: An efficient virtual knockout tool for gene function predictions via single-cell gene regulatory network perturbation

“…Both Krcc1 and Rps8 have been reported to play a role in regulating cellular plasticity and fibrotic process. 34,35 Duchenne muscular dystrophy Duchenne muscular dystrophy (DMD) arises as a result of mutations in the open reading frame of DMD. 36,37 The DMD gene encodes dystrophin, a large cytoskeletal structural protein, mostly absent in DMD patients.…”