CPSF1 inhibition promotes widespread use of intergenic polyadenylation sites and impairs glycolysis in prostate cancer cells
Summary: Localized prostate cancer can be cured by radiation or surgery, but advanced prostate cancer continues to be a clinical challenge. Altered alternative polyadenylation occurs in numerous cancers and can downregulate tumor-suppressor genes and upregulate oncogenes. We found that the cleavage...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-01-01
|
| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124724015626 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832590015705645056 |
|---|---|
| author | Kiel T. Tietz Braedan M. McCluskey Conor R. Miller Yingming Li Sarah A. Munro Scott M. Dehm |
| author_facet | Kiel T. Tietz Braedan M. McCluskey Conor R. Miller Yingming Li Sarah A. Munro Scott M. Dehm |
| author_sort | Kiel T. Tietz |
| collection | DOAJ |
| description | Summary: Localized prostate cancer can be cured by radiation or surgery, but advanced prostate cancer continues to be a clinical challenge. Altered alternative polyadenylation occurs in numerous cancers and can downregulate tumor-suppressor genes and upregulate oncogenes. We found that the cleavage and polyadenylation specificity factor (CPSF) complex factor CPSF1 is upregulated in patients with advanced prostate cancer, with high CPSF1 expression correlating with worse progression-free survival. Knockdown of CPSF1 selectively inhibited the growth of prostate cancer cells and reduced glycolytic output. Evaluating the changes in global poly(A) site usage in prostate cancer cells following CPSF1 knockdown revealed widespread usage of intergenic poly(A) sites distal to annotated 3′ UTRs, which lengthened 3′ UTRs and decreased levels of thousands of mRNAs, including key glycolysis genes. These findings uncover a role for CPSF1 in the suppression of intergenic poly(A) sites in prostate cancer and nominate CPSF1 as a therapeutic target in advanced prostate cancer. |
| format | Article |
| id | doaj-art-e4e69a6eeedc438cb26177958c2f2923 |
| institution | Kabale University |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-e4e69a6eeedc438cb26177958c2f29232025-01-24T04:44:59ZengElsevierCell Reports2211-12472025-01-01441115211CPSF1 inhibition promotes widespread use of intergenic polyadenylation sites and impairs glycolysis in prostate cancer cellsKiel T. Tietz0Braedan M. McCluskey1Conor R. Miller2Yingming Li3Sarah A. Munro4Scott M. Dehm5Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USAMinnesota Supercomputing Institute, University of Minnesota, Minneapolis, MN 55455, USAMasonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USAMasonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USAMinnesota Supercomputing Institute, University of Minnesota, Minneapolis, MN 55455, USAMasonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA; Corresponding authorSummary: Localized prostate cancer can be cured by radiation or surgery, but advanced prostate cancer continues to be a clinical challenge. Altered alternative polyadenylation occurs in numerous cancers and can downregulate tumor-suppressor genes and upregulate oncogenes. We found that the cleavage and polyadenylation specificity factor (CPSF) complex factor CPSF1 is upregulated in patients with advanced prostate cancer, with high CPSF1 expression correlating with worse progression-free survival. Knockdown of CPSF1 selectively inhibited the growth of prostate cancer cells and reduced glycolytic output. Evaluating the changes in global poly(A) site usage in prostate cancer cells following CPSF1 knockdown revealed widespread usage of intergenic poly(A) sites distal to annotated 3′ UTRs, which lengthened 3′ UTRs and decreased levels of thousands of mRNAs, including key glycolysis genes. These findings uncover a role for CPSF1 in the suppression of intergenic poly(A) sites in prostate cancer and nominate CPSF1 as a therapeutic target in advanced prostate cancer.http://www.sciencedirect.com/science/article/pii/S2211124724015626CP: CancerCP: Molecular biology |
| spellingShingle | Kiel T. Tietz Braedan M. McCluskey Conor R. Miller Yingming Li Sarah A. Munro Scott M. Dehm CPSF1 inhibition promotes widespread use of intergenic polyadenylation sites and impairs glycolysis in prostate cancer cells Cell Reports CP: Cancer CP: Molecular biology |
| title | CPSF1 inhibition promotes widespread use of intergenic polyadenylation sites and impairs glycolysis in prostate cancer cells |
| title_full | CPSF1 inhibition promotes widespread use of intergenic polyadenylation sites and impairs glycolysis in prostate cancer cells |
| title_fullStr | CPSF1 inhibition promotes widespread use of intergenic polyadenylation sites and impairs glycolysis in prostate cancer cells |
| title_full_unstemmed | CPSF1 inhibition promotes widespread use of intergenic polyadenylation sites and impairs glycolysis in prostate cancer cells |
| title_short | CPSF1 inhibition promotes widespread use of intergenic polyadenylation sites and impairs glycolysis in prostate cancer cells |
| title_sort | cpsf1 inhibition promotes widespread use of intergenic polyadenylation sites and impairs glycolysis in prostate cancer cells |
| topic | CP: Cancer CP: Molecular biology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124724015626 |
| work_keys_str_mv | AT kielttietz cpsf1inhibitionpromoteswidespreaduseofintergenicpolyadenylationsitesandimpairsglycolysisinprostatecancercells AT braedanmmccluskey cpsf1inhibitionpromoteswidespreaduseofintergenicpolyadenylationsitesandimpairsglycolysisinprostatecancercells AT conorrmiller cpsf1inhibitionpromoteswidespreaduseofintergenicpolyadenylationsitesandimpairsglycolysisinprostatecancercells AT yingmingli cpsf1inhibitionpromoteswidespreaduseofintergenicpolyadenylationsitesandimpairsglycolysisinprostatecancercells AT sarahamunro cpsf1inhibitionpromoteswidespreaduseofintergenicpolyadenylationsitesandimpairsglycolysisinprostatecancercells AT scottmdehm cpsf1inhibitionpromoteswidespreaduseofintergenicpolyadenylationsitesandimpairsglycolysisinprostatecancercells |