C20orf204, a hepatocellular carcinoma-specific protein interacts with nucleolin and promotes cell proliferation
Abstract In most human cancers, a large number of proteins with driver mutations are involved in tumor development, implying that multiple fine tuners are involved in cancer formation and/or maintenance. A useful strategy for cancer therapy may therefore be to target multiple cancer type-specific fi...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2021-03-01
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| Series: | Oncogenesis |
| Online Access: | https://doi.org/10.1038/s41389-021-00320-3 |
| _version_ | 1818673344947421184 |
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| author | Sebastian Burbano De Lara Doan Duy Hai Tran Aldrige Bernardus Allister Mareike Polenkowski Björn Nashan Martina Koch Teruko Tamura |
| author_facet | Sebastian Burbano De Lara Doan Duy Hai Tran Aldrige Bernardus Allister Mareike Polenkowski Björn Nashan Martina Koch Teruko Tamura |
| author_sort | Sebastian Burbano De Lara |
| collection | DOAJ |
| description | Abstract In most human cancers, a large number of proteins with driver mutations are involved in tumor development, implying that multiple fine tuners are involved in cancer formation and/or maintenance. A useful strategy for cancer therapy may therefore be to target multiple cancer type-specific fine tuners. Furthermore, genome-wide association studies of tumor samples have identified a large number of long noncoding (lnc)RNA associated with various types of tumor. In this context we have previously found that C20orf204 (a splice variant of Linc00176) RNA contains a 189 amino acid (AA) long open reading frame (C20orf204-189AA) that is expressed predominantly in hepatocellular carcinoma (HCC). We report here that a protein, C20orf204-189AA, was detected in the nucleus of 14 out of 20 primary HCC, but not in control livers. Strikingly, overexpression of C20orf204-189AA enhanced cell proliferation and ribosomal RNA transcription. C20orf204-189AA is co-localized, and interacted with nucleolin via the C-terminal and with ribosomal RNA via the N-terminal domain. Furthermore, the expression of C20orf204-189AA upregulates the protein level of nucleolin. Nucleolin and C20orf204 mRNA levels in HCC are correlated with tumor differentiation grade and patient survival, suggesting that C20orf204-189AA is a cancer type-specific fine tuner in some HCC that presents itself for potential targeting therapy and cancer biomarker. Thus, cancer cells exhibit remarkable transcriptome alterations partly by adopting cancer-specific splicing isoforms of noncoding RNAs and may participate in tumor development. |
| first_indexed | 2024-12-17T07:54:18Z |
| format | Article |
| id | doaj.art-288db5e2b36742e9a1c895822e665bf1 |
| institution | Directory Open Access Journal |
| issn | 2157-9024 |
| language | English |
| last_indexed | 2024-12-17T07:54:18Z |
| publishDate | 2021-03-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Oncogenesis |
| spelling | doaj.art-288db5e2b36742e9a1c895822e665bf12022-12-21T21:57:46ZengNature Publishing GroupOncogenesis2157-90242021-03-0110311310.1038/s41389-021-00320-3C20orf204, a hepatocellular carcinoma-specific protein interacts with nucleolin and promotes cell proliferationSebastian Burbano De Lara0Doan Duy Hai Tran1Aldrige Bernardus Allister2Mareike Polenkowski3Björn Nashan4Martina Koch5Teruko Tamura6Institut fuer Zellbiochemie, OE4310, Medizinische Hochschule HannoverInstitut fuer Zellbiochemie, OE4310, Medizinische Hochschule HannoverInstitut fuer Zellbiochemie, OE4310, Medizinische Hochschule HannoverInstitut fuer Zellbiochemie, OE4310, Medizinische Hochschule HannoverDepartment of Hepatobiliary and Transplant Surgery, University Medical Center EppendorfDepartment of Hepatobiliary and Transplant Surgery, University Medical Center EppendorfInstitut fuer Zellbiochemie, OE4310, Medizinische Hochschule HannoverAbstract In most human cancers, a large number of proteins with driver mutations are involved in tumor development, implying that multiple fine tuners are involved in cancer formation and/or maintenance. A useful strategy for cancer therapy may therefore be to target multiple cancer type-specific fine tuners. Furthermore, genome-wide association studies of tumor samples have identified a large number of long noncoding (lnc)RNA associated with various types of tumor. In this context we have previously found that C20orf204 (a splice variant of Linc00176) RNA contains a 189 amino acid (AA) long open reading frame (C20orf204-189AA) that is expressed predominantly in hepatocellular carcinoma (HCC). We report here that a protein, C20orf204-189AA, was detected in the nucleus of 14 out of 20 primary HCC, but not in control livers. Strikingly, overexpression of C20orf204-189AA enhanced cell proliferation and ribosomal RNA transcription. C20orf204-189AA is co-localized, and interacted with nucleolin via the C-terminal and with ribosomal RNA via the N-terminal domain. Furthermore, the expression of C20orf204-189AA upregulates the protein level of nucleolin. Nucleolin and C20orf204 mRNA levels in HCC are correlated with tumor differentiation grade and patient survival, suggesting that C20orf204-189AA is a cancer type-specific fine tuner in some HCC that presents itself for potential targeting therapy and cancer biomarker. Thus, cancer cells exhibit remarkable transcriptome alterations partly by adopting cancer-specific splicing isoforms of noncoding RNAs and may participate in tumor development.https://doi.org/10.1038/s41389-021-00320-3 |
| spellingShingle | Sebastian Burbano De Lara Doan Duy Hai Tran Aldrige Bernardus Allister Mareike Polenkowski Björn Nashan Martina Koch Teruko Tamura C20orf204, a hepatocellular carcinoma-specific protein interacts with nucleolin and promotes cell proliferation Oncogenesis |
| title | C20orf204, a hepatocellular carcinoma-specific protein interacts with nucleolin and promotes cell proliferation |
| title_full | C20orf204, a hepatocellular carcinoma-specific protein interacts with nucleolin and promotes cell proliferation |
| title_fullStr | C20orf204, a hepatocellular carcinoma-specific protein interacts with nucleolin and promotes cell proliferation |
| title_full_unstemmed | C20orf204, a hepatocellular carcinoma-specific protein interacts with nucleolin and promotes cell proliferation |
| title_short | C20orf204, a hepatocellular carcinoma-specific protein interacts with nucleolin and promotes cell proliferation |
| title_sort | c20orf204 a hepatocellular carcinoma specific protein interacts with nucleolin and promotes cell proliferation |
| url | https://doi.org/10.1038/s41389-021-00320-3 |
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