Complementary analysis of proteome‐wide proteomics reveals changes in RNA binding protein‐profiles during prostate cancer progression
Abstract Background Accumulating evidence indicates importance of RNA regulation in cancer. This includes events such as splicing, translation, and regulation of noncoding RNAs, functions which are governed by RNA binding proteins (RBPs). Aims To find which RBPs could be relevant for prostate cancer...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-10-01
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| Series: | Cancer Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cnr2.1886 |
| _version_ | 1797650746989084672 |
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| author | Erika Aikio Sonja Koivukoski Elina Kallio Nithin Sadeesh Einari A. Niskanen Leena Latonen |
| author_facet | Erika Aikio Sonja Koivukoski Elina Kallio Nithin Sadeesh Einari A. Niskanen Leena Latonen |
| author_sort | Erika Aikio |
| collection | DOAJ |
| description | Abstract Background Accumulating evidence indicates importance of RNA regulation in cancer. This includes events such as splicing, translation, and regulation of noncoding RNAs, functions which are governed by RNA binding proteins (RBPs). Aims To find which RBPs could be relevant for prostate cancer, we performed systematic screening of RBP expression in clinical prostate cancer. Methods and Results We interrogated four proteome‐wide proteomics datasets including tumor samples of primary, castration resistant, and metastatic prostate cancer. We found that, while the majority of RBPs are expressed but not significantly altered during prostate cancer development and progression, expression of several RBPs increases in advanced disease. Interestingly, most of the differentially expressed RBPs are not targets of differential posttranscriptional phosphorylation during disease progression. The RBPs undergoing expression changes have functions in, especially, poly(A)‐RNA binding, nucleocytoplasmic transport, and cellular stress responses, suggesting that these may play a role in formation of castration resistance. Pathway analyzes indicate that increased ribosome production and chromatin‐related functions of RBPs are also linked to castration resistant and metastatic prostate cancers. We selected a group of differentially expressed RBPs and studied their role in cultured prostate cancer cells. With siRNA screens, several of these were indicated in survival (DDX6, EIF4A3, PABPN1), growth (e.g., EIF5A, HNRNPH2, LRRC47, and NVL), and migration (e.g., NOL3 and SLTM) of prostate cancer cells. Our analyzes further show that RRP9, a U3 small nucleolar protein essential for ribosome formation, undergoes changes at protein level during metastasis in prostate cancer. Conclusion In this work, we recognized significant molecular alterations in RBP profiles during development and evolution of prostate cancer. Our study further indicates several functionally significant RBPs warranting further investigation for their functions and possible targetability in prostate cancer. |
| first_indexed | 2024-03-11T16:05:54Z |
| format | Article |
| id | doaj.art-352d6ac8ad3d4738847cd30c187c7ad2 |
| institution | Directory Open Access Journal |
| issn | 2573-8348 |
| language | English |
| last_indexed | 2024-03-11T16:05:54Z |
| publishDate | 2023-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Reports |
| spelling | doaj.art-352d6ac8ad3d4738847cd30c187c7ad22023-10-25T03:24:42ZengWileyCancer Reports2573-83482023-10-01610n/an/a10.1002/cnr2.1886Complementary analysis of proteome‐wide proteomics reveals changes in RNA binding protein‐profiles during prostate cancer progressionErika Aikio0Sonja Koivukoski1Elina Kallio2Nithin Sadeesh3Einari A. Niskanen4Leena Latonen5Institute of Biomedicine University of Eastern Finland Kuopio FinlandInstitute of Biomedicine University of Eastern Finland Kuopio FinlandInstitute of Biomedicine University of Eastern Finland Kuopio FinlandInstitute of Biomedicine University of Eastern Finland Kuopio FinlandInstitute of Biomedicine University of Eastern Finland Kuopio FinlandInstitute of Biomedicine University of Eastern Finland Kuopio FinlandAbstract Background Accumulating evidence indicates importance of RNA regulation in cancer. This includes events such as splicing, translation, and regulation of noncoding RNAs, functions which are governed by RNA binding proteins (RBPs). Aims To find which RBPs could be relevant for prostate cancer, we performed systematic screening of RBP expression in clinical prostate cancer. Methods and Results We interrogated four proteome‐wide proteomics datasets including tumor samples of primary, castration resistant, and metastatic prostate cancer. We found that, while the majority of RBPs are expressed but not significantly altered during prostate cancer development and progression, expression of several RBPs increases in advanced disease. Interestingly, most of the differentially expressed RBPs are not targets of differential posttranscriptional phosphorylation during disease progression. The RBPs undergoing expression changes have functions in, especially, poly(A)‐RNA binding, nucleocytoplasmic transport, and cellular stress responses, suggesting that these may play a role in formation of castration resistance. Pathway analyzes indicate that increased ribosome production and chromatin‐related functions of RBPs are also linked to castration resistant and metastatic prostate cancers. We selected a group of differentially expressed RBPs and studied their role in cultured prostate cancer cells. With siRNA screens, several of these were indicated in survival (DDX6, EIF4A3, PABPN1), growth (e.g., EIF5A, HNRNPH2, LRRC47, and NVL), and migration (e.g., NOL3 and SLTM) of prostate cancer cells. Our analyzes further show that RRP9, a U3 small nucleolar protein essential for ribosome formation, undergoes changes at protein level during metastasis in prostate cancer. Conclusion In this work, we recognized significant molecular alterations in RBP profiles during development and evolution of prostate cancer. Our study further indicates several functionally significant RBPs warranting further investigation for their functions and possible targetability in prostate cancer.https://doi.org/10.1002/cnr2.1886castration resistancemetastasisprostate cancerRNA binding proteins |
| spellingShingle | Erika Aikio Sonja Koivukoski Elina Kallio Nithin Sadeesh Einari A. Niskanen Leena Latonen Complementary analysis of proteome‐wide proteomics reveals changes in RNA binding protein‐profiles during prostate cancer progression Cancer Reports castration resistance metastasis prostate cancer RNA binding proteins |
| title | Complementary analysis of proteome‐wide proteomics reveals changes in RNA binding protein‐profiles during prostate cancer progression |
| title_full | Complementary analysis of proteome‐wide proteomics reveals changes in RNA binding protein‐profiles during prostate cancer progression |
| title_fullStr | Complementary analysis of proteome‐wide proteomics reveals changes in RNA binding protein‐profiles during prostate cancer progression |
| title_full_unstemmed | Complementary analysis of proteome‐wide proteomics reveals changes in RNA binding protein‐profiles during prostate cancer progression |
| title_short | Complementary analysis of proteome‐wide proteomics reveals changes in RNA binding protein‐profiles during prostate cancer progression |
| title_sort | complementary analysis of proteome wide proteomics reveals changes in rna binding protein profiles during prostate cancer progression |
| topic | castration resistance metastasis prostate cancer RNA binding proteins |
| url | https://doi.org/10.1002/cnr2.1886 |
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