Abstract
Overexpression of centromeric proteins has been identified in a number of human malignancies, but the functional and mechanistic contributions of these proteins to disease progression have not been characterized. The centromeric histone H3 variant centromere protein A (CENPA) is an epigenetic mark that determines centromere identity. Here, using an array of approaches, including RNA-sequencing and ChIP-sequencing analyses, immunohistochemistry-based tissue microarrays, and various cell biology assays, we demonstrate that CENPA is highly overexpressed in prostate cancer in both tissue and cell lines and that the level of CENPA expression correlates with the disease stage in a large cohort of patients. Gain-of-function and loss-of-function experiments confirmed that CENPA promotes prostate cancer cell line growth. The results from the integrated sequencing experiments suggested a previously unidentified function of CENPA as a transcriptional regulator that modulates expression of critical proliferation, cell-cycle, and centromere/kinetochore genes. Taken together, our findings show that CENPA overexpression is crucial to prostate cancer growth.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 8537-8549 |
| Number of pages | 13 |
| Journal | Journal of Biological Chemistry |
| Volume | 295 |
| Issue number | 25 |
| DOIs | |
| State | Published - Jun 19 2020 |
Bibliographical note
Funding Information:and T. T.), R01-CA-158286-S1 (to M. A. S.), and RM-08-029 and P30U54ES017885 (to G. S. O.); a University of Michigan Cancer Biology Fellowship (to A. K. S.); the Scleroderma Foundation (to R. C.-G.); Prostate Cancer Foundation Grant 17YOUN13 (to Y. S. N.); the Biomedical Research Core Facilities Epigenomics Core at the University of Michigan (to T. Q. and K. P.); the A. Alfred Taubman Medical Research Institute (to S. A. T.); a Howard Hughes Medical Institute Investigatorship (to A. M. C.); an A. Alfred Taubman Scholarship (to A. M. C.); and an American Cancer Society Professorship (to A. M. C.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Funding Information:
Funding and additional information—This work was supported by National Institutes of Health Grants R01-DK109188 (to D. M. M.), 5T32GM007863-34 and F30-CA-210379 (to A. K. S.), F30-CA-200328 (to Y. S. N.), R01-DK109188 (to M. P., C. W., B. Q., E. W.,
Publisher Copyright:
© 2020 Saha et al. Published by The American Society for Biochemistry and Molecular Biology, Inc.
