RepID as a potential biomarker and therapeutic target for lung neuroendocrine tumor
Abstract Neuroendocrine tumor (NET) is a rare malignant tumor, notably small cell lung cancer (SCLC), a type of lung neuroendocrine tumor, which has a survival rate of less than 7%. Although various biomarkers including CHGA (Chromogranin A), INSM1 (Insulinoma-associated protein 1), and SYP (Synapto...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-11-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-024-79104-9 |
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| author | Jong-Uk Park Jae-Hyun Jo Sangjune Kim Christophe E. Redon Mirit I. Aladjem Yuri Seo Se Jin Jang Sang-Min Jang |
| author_facet | Jong-Uk Park Jae-Hyun Jo Sangjune Kim Christophe E. Redon Mirit I. Aladjem Yuri Seo Se Jin Jang Sang-Min Jang |
| author_sort | Jong-Uk Park |
| collection | DOAJ |
| description | Abstract Neuroendocrine tumor (NET) is a rare malignant tumor, notably small cell lung cancer (SCLC), a type of lung neuroendocrine tumor, which has a survival rate of less than 7%. Although various biomarkers including CHGA (Chromogranin A), INSM1 (Insulinoma-associated protein 1), and SYP (Synaptophysin) are extensively used for the diagnostic testing of NET, their diverse specificities and sensitivities are acknowledged as limitations. Here, we demonstrate that RepID (Replication initiation determinant protein), a component of CRL4 (Cullin-RING ubiquitin E3 ligase 4), holds promise as a biomarker for identifying NET and SCLC. Analysis of the Cancer Cell Line Encyclopedia (CCLE) via the CellMinerCDB portal reveals a high correlation between RepID transcript levels and mRNA expression of NE signature genes. Additionally, RepID protein is highly expressed in SCLC patient tissues and a subset of SCLC cell lines. Viability analysis following treatment with pevonedistat and SZL-P1-41 in SCLC cell lines and human SCLC-organoid models indicates that RepID expression determines the sensitivity to CRL-targeting anti-cancer drugs. These findings suggest that RepID represents a novel biomarker for NET and SCLC, and insights from RepID research in these cancers could lead to innovative therapeutic strategies. |
| format | Article |
| id | doaj-art-914d4610c8ac474cb06d2331a2f7b7a5 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-914d4610c8ac474cb06d2331a2f7b7a52024-11-17T12:18:09ZengNature PortfolioScientific Reports2045-23222024-11-0114111010.1038/s41598-024-79104-9RepID as a potential biomarker and therapeutic target for lung neuroendocrine tumorJong-Uk Park0Jae-Hyun Jo1Sangjune Kim2Christophe E. Redon3Mirit I. Aladjem4Yuri Seo5Se Jin Jang6Sang-Min Jang7Department of Biochemistry, Chungbuk National UniversityDepartment of Biochemistry, Chungbuk National UniversityDepartment of Biological Sciences and Biotechnology, Chungbuk National UniversityDevelopmental Therapeutics Branch, Center for Cancer Research, NCI, NIHDevelopmental Therapeutics Branch, Center for Cancer Research, NCI, NIHSG Medical Inc.SG Medical Inc.Department of Biochemistry, Chungbuk National UniversityAbstract Neuroendocrine tumor (NET) is a rare malignant tumor, notably small cell lung cancer (SCLC), a type of lung neuroendocrine tumor, which has a survival rate of less than 7%. Although various biomarkers including CHGA (Chromogranin A), INSM1 (Insulinoma-associated protein 1), and SYP (Synaptophysin) are extensively used for the diagnostic testing of NET, their diverse specificities and sensitivities are acknowledged as limitations. Here, we demonstrate that RepID (Replication initiation determinant protein), a component of CRL4 (Cullin-RING ubiquitin E3 ligase 4), holds promise as a biomarker for identifying NET and SCLC. Analysis of the Cancer Cell Line Encyclopedia (CCLE) via the CellMinerCDB portal reveals a high correlation between RepID transcript levels and mRNA expression of NE signature genes. Additionally, RepID protein is highly expressed in SCLC patient tissues and a subset of SCLC cell lines. Viability analysis following treatment with pevonedistat and SZL-P1-41 in SCLC cell lines and human SCLC-organoid models indicates that RepID expression determines the sensitivity to CRL-targeting anti-cancer drugs. These findings suggest that RepID represents a novel biomarker for NET and SCLC, and insights from RepID research in these cancers could lead to innovative therapeutic strategies.https://doi.org/10.1038/s41598-024-79104-9Neuroendocrine tumorSmall cell lung cancerRepIDCRL |
| spellingShingle | Jong-Uk Park Jae-Hyun Jo Sangjune Kim Christophe E. Redon Mirit I. Aladjem Yuri Seo Se Jin Jang Sang-Min Jang RepID as a potential biomarker and therapeutic target for lung neuroendocrine tumor Scientific Reports Neuroendocrine tumor Small cell lung cancer RepID CRL |
| title | RepID as a potential biomarker and therapeutic target for lung neuroendocrine tumor |
| title_full | RepID as a potential biomarker and therapeutic target for lung neuroendocrine tumor |
| title_fullStr | RepID as a potential biomarker and therapeutic target for lung neuroendocrine tumor |
| title_full_unstemmed | RepID as a potential biomarker and therapeutic target for lung neuroendocrine tumor |
| title_short | RepID as a potential biomarker and therapeutic target for lung neuroendocrine tumor |
| title_sort | repid as a potential biomarker and therapeutic target for lung neuroendocrine tumor |
| topic | Neuroendocrine tumor Small cell lung cancer RepID CRL |
| url | https://doi.org/10.1038/s41598-024-79104-9 |
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