RBM5 reduces small cell lung cancer growth, increases cisplatin sensitivity and regulates key transformation-associated pathways
Small cell lung cancer (SCLC) is the most aggressive type of lung cancer, with almost 95% of patients succumbing to the disease. Although RBM5, a tumor suppressor gene, is downregulated in the majority of lung cancers, its role in SCLC is unknown. Using the GLC20 SCLC cell line, which has a homozygo...
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| Format: | Article |
| Language: | English |
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Elsevier
2016-11-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844016315808 |
| _version_ | 1811214803743539200 |
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| author | Julie J. Loiselle Justin G. Roy Leslie C. Sutherland |
| author_facet | Julie J. Loiselle Justin G. Roy Leslie C. Sutherland |
| author_sort | Julie J. Loiselle |
| collection | DOAJ |
| description | Small cell lung cancer (SCLC) is the most aggressive type of lung cancer, with almost 95% of patients succumbing to the disease. Although RBM5, a tumor suppressor gene, is downregulated in the majority of lung cancers, its role in SCLC is unknown. Using the GLC20 SCLC cell line, which has a homozygous deletion encompassing the RBM5 gene locus, we established stable RBM5 expressing sublines and investigated the effects of RBM5 re-expression. Transcriptome and target identification studies determined that RBM5 directly regulates the cell cycle and apoptosis in SCLC cells, as well as significantly downregulates other important transformation-associated pathways such as angiogenesis and cell adhesion. RNA sequencing of paired non-tumor and tumor SCLC patient specimens showed decreased RBM5 expression in the tumors, and expression alterations in the majority of the same pathways that were altered in the GLC20 cells and sublines. Functional studies confirmed RBM5 expression slows SCLC cell line growth, and increases sensitivity to the chemotherapy drug cisplatin. Overall, our work demonstrates the importance of RBM5 expression to the non-transformed state of lung cells and the consequences of its deletion to SCLC development and progression. |
| first_indexed | 2024-04-12T06:10:42Z |
| format | Article |
| id | doaj.art-919ed0ce912f4e699f0f7f4caf73aa67 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-04-12T06:10:42Z |
| publishDate | 2016-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-919ed0ce912f4e699f0f7f4caf73aa672022-12-22T03:44:42ZengElsevierHeliyon2405-84402016-11-0121110.1016/j.heliyon.2016.e00204RBM5 reduces small cell lung cancer growth, increases cisplatin sensitivity and regulates key transformation-associated pathwaysJulie J. Loiselle0Justin G. Roy1Leslie C. Sutherland2Biomolecular Sciences Program, Laurentian University, Sudbury, ON P3E 2C6, CanadaDepartment of Chemistry and Biochemistry, Laurentian University, Sudbury, ON P3E 2C6, CanadaBiomolecular Sciences Program, Laurentian University, Sudbury, ON P3E 2C6, CanadaSmall cell lung cancer (SCLC) is the most aggressive type of lung cancer, with almost 95% of patients succumbing to the disease. Although RBM5, a tumor suppressor gene, is downregulated in the majority of lung cancers, its role in SCLC is unknown. Using the GLC20 SCLC cell line, which has a homozygous deletion encompassing the RBM5 gene locus, we established stable RBM5 expressing sublines and investigated the effects of RBM5 re-expression. Transcriptome and target identification studies determined that RBM5 directly regulates the cell cycle and apoptosis in SCLC cells, as well as significantly downregulates other important transformation-associated pathways such as angiogenesis and cell adhesion. RNA sequencing of paired non-tumor and tumor SCLC patient specimens showed decreased RBM5 expression in the tumors, and expression alterations in the majority of the same pathways that were altered in the GLC20 cells and sublines. Functional studies confirmed RBM5 expression slows SCLC cell line growth, and increases sensitivity to the chemotherapy drug cisplatin. Overall, our work demonstrates the importance of RBM5 expression to the non-transformed state of lung cells and the consequences of its deletion to SCLC development and progression.http://www.sciencedirect.com/science/article/pii/S2405844016315808Cancer researchCell biology |
| spellingShingle | Julie J. Loiselle Justin G. Roy Leslie C. Sutherland RBM5 reduces small cell lung cancer growth, increases cisplatin sensitivity and regulates key transformation-associated pathways Heliyon Cancer research Cell biology |
| title | RBM5 reduces small cell lung cancer growth, increases cisplatin sensitivity and regulates key transformation-associated pathways |
| title_full | RBM5 reduces small cell lung cancer growth, increases cisplatin sensitivity and regulates key transformation-associated pathways |
| title_fullStr | RBM5 reduces small cell lung cancer growth, increases cisplatin sensitivity and regulates key transformation-associated pathways |
| title_full_unstemmed | RBM5 reduces small cell lung cancer growth, increases cisplatin sensitivity and regulates key transformation-associated pathways |
| title_short | RBM5 reduces small cell lung cancer growth, increases cisplatin sensitivity and regulates key transformation-associated pathways |
| title_sort | rbm5 reduces small cell lung cancer growth increases cisplatin sensitivity and regulates key transformation associated pathways |
| topic | Cancer research Cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S2405844016315808 |
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