Differential Expression of RSK4 Transcript Isoforms in Cancer and Its Clinical Relevance
While we previously revealed RSK4 as a therapeutic target in lung and bladder cancers, the wider role of this kinase in other cancers remains controversial. Indeed, other reports instead proposed RSK4 as a tumour suppressor in colorectal and gastric cancers and are contradictory in breast malignanci...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/23/14569 |
| _version_ | 1797463179659313152 |
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| author | Sisi Chen Michael J. Seckl Marc P. G. Lorentzen Olivier E. Pardo |
| author_facet | Sisi Chen Michael J. Seckl Marc P. G. Lorentzen Olivier E. Pardo |
| author_sort | Sisi Chen |
| collection | DOAJ |
| description | While we previously revealed RSK4 as a therapeutic target in lung and bladder cancers, the wider role of this kinase in other cancers remains controversial. Indeed, other reports instead proposed RSK4 as a tumour suppressor in colorectal and gastric cancers and are contradictory in breast malignancies. One explanation for these discrepancies may be the expression of different RSK4 isoforms across cancers. Four RNAs are produced from the RSK4 gene, with two being protein-coding. Here, we analysed the expression of the latter across 30 normal and 33 cancer tissue types from the combined GTEx/TCGA dataset and correlated it with clinical features. This revealed the expression of RSK4 isoforms 1 and 2 to be independent prognostic factors for patient survival, pathological stage, cancer metastasis, recurrence, and immune infiltration in brain, stomach, cervical, and kidney cancers. However, we found that upregulation of either isoform can equally be associated with good or bad prognosis depending on the cancer type, and changes in the expression ratio of isoforms fail to predict clinical outcome. Hence, differential isoform expression alone cannot explain the contradictory roles of RSK4 in cancers, and further research is needed to highlight the underlying mechanisms for the context-dependent function of this kinase. |
| first_indexed | 2024-03-09T17:47:59Z |
| format | Article |
| id | doaj.art-f56d0123f3be4c9d85fd79d048a3f5c9 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T17:47:59Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-f56d0123f3be4c9d85fd79d048a3f5c92023-11-24T11:04:14ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-11-0123231456910.3390/ijms232314569Differential Expression of RSK4 Transcript Isoforms in Cancer and Its Clinical RelevanceSisi Chen0Michael J. Seckl1Marc P. G. Lorentzen2Olivier E. Pardo3Division of Cancer, Department of Surgery & Cancer, Hammersmith Campus, Imperial College London, London W12 0NN, UKDivision of Cancer, Department of Surgery & Cancer, Hammersmith Campus, Imperial College London, London W12 0NN, UKDivision of Cancer, Department of Surgery & Cancer, Hammersmith Campus, Imperial College London, London W12 0NN, UKDivision of Cancer, Department of Surgery & Cancer, Hammersmith Campus, Imperial College London, London W12 0NN, UKWhile we previously revealed RSK4 as a therapeutic target in lung and bladder cancers, the wider role of this kinase in other cancers remains controversial. Indeed, other reports instead proposed RSK4 as a tumour suppressor in colorectal and gastric cancers and are contradictory in breast malignancies. One explanation for these discrepancies may be the expression of different RSK4 isoforms across cancers. Four RNAs are produced from the RSK4 gene, with two being protein-coding. Here, we analysed the expression of the latter across 30 normal and 33 cancer tissue types from the combined GTEx/TCGA dataset and correlated it with clinical features. This revealed the expression of RSK4 isoforms 1 and 2 to be independent prognostic factors for patient survival, pathological stage, cancer metastasis, recurrence, and immune infiltration in brain, stomach, cervical, and kidney cancers. However, we found that upregulation of either isoform can equally be associated with good or bad prognosis depending on the cancer type, and changes in the expression ratio of isoforms fail to predict clinical outcome. Hence, differential isoform expression alone cannot explain the contradictory roles of RSK4 in cancers, and further research is needed to highlight the underlying mechanisms for the context-dependent function of this kinase.https://www.mdpi.com/1422-0067/23/23/14569RSK4<i>RPS6KA6</i>isoformsnormal tissuecancerprognosis |
| spellingShingle | Sisi Chen Michael J. Seckl Marc P. G. Lorentzen Olivier E. Pardo Differential Expression of RSK4 Transcript Isoforms in Cancer and Its Clinical Relevance International Journal of Molecular Sciences RSK4 <i>RPS6KA6</i> isoforms normal tissue cancer prognosis |
| title | Differential Expression of RSK4 Transcript Isoforms in Cancer and Its Clinical Relevance |
| title_full | Differential Expression of RSK4 Transcript Isoforms in Cancer and Its Clinical Relevance |
| title_fullStr | Differential Expression of RSK4 Transcript Isoforms in Cancer and Its Clinical Relevance |
| title_full_unstemmed | Differential Expression of RSK4 Transcript Isoforms in Cancer and Its Clinical Relevance |
| title_short | Differential Expression of RSK4 Transcript Isoforms in Cancer and Its Clinical Relevance |
| title_sort | differential expression of rsk4 transcript isoforms in cancer and its clinical relevance |
| topic | RSK4 <i>RPS6KA6</i> isoforms normal tissue cancer prognosis |
| url | https://www.mdpi.com/1422-0067/23/23/14569 |
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