Molecular Signature of Small Cell Lung Cancer after Treatment Failure: The <i>MCM</i> Complex as Therapeutic Target
Small cell lung cancer (SCLC) is a highly aggressive cancer, and patients who become refractory to first-line treatment have a poor prognosis. The development of effective treatment regimens is urgently needed. In this study, we identified a gene expression signature of SCLC after treatment failure...
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MDPI AG
2021-03-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/6/1187 |
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| author | Shunsuke Misono Keiko Mizuno Takayuki Suetsugu Kengo Tanigawa Nijiro Nohata Akifumi Uchida Hiroki Sanada Reona Okada Shogo Moriya Hiromasa Inoue Naohiko Seki |
| author_facet | Shunsuke Misono Keiko Mizuno Takayuki Suetsugu Kengo Tanigawa Nijiro Nohata Akifumi Uchida Hiroki Sanada Reona Okada Shogo Moriya Hiromasa Inoue Naohiko Seki |
| author_sort | Shunsuke Misono |
| collection | DOAJ |
| description | Small cell lung cancer (SCLC) is a highly aggressive cancer, and patients who become refractory to first-line treatment have a poor prognosis. The development of effective treatment regimens is urgently needed. In this study, we identified a gene expression signature of SCLC after treatment failure using SCLC clinical specimens (GEO accession number: GSE162102). A total of 1,136 genes were significantly upregulated in SCLC tissues. These upregulated genes were subjected to KEGG pathway analysis, and “cell cycle”, “Fanconi anemia”, “alcoholism”, “systemic lupus erythematosus”, “oocyte meiosis”, “homologous recombination”, “DNA replication”, and “p53 signaling” were identified as the enriched pathways among the genes. We focused on the cell cycle pathway and investigated the clinical significance of four genes associated with this pathway: minichromosome maintenance (<i>MCM</i>) 2, <i>MCM4</i>, <i>MCM6</i>, and <i>MCM7</i>. The overexpression of these <i>MCM</i> genes was confirmed in SCLC clinical specimens. Knockdown assays using siRNAs targeting each of these four <i>MCM</i> genes showed significant attenuation of cancer cell proliferation. Moreover, siRNA-mediated knockdown of each <i>MCM</i> gene enhanced the cisplatin sensitivity of SCLC cells. Our SCLC molecular signature based on SCLC clinical specimens after treatment failure will provide useful information to identify novel molecular targets for this disease. |
| first_indexed | 2024-03-10T13:23:01Z |
| format | Article |
| id | doaj.art-364cc3d851714db69029919b6c12d22b |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T13:23:01Z |
| publishDate | 2021-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-364cc3d851714db69029919b6c12d22b2023-11-21T09:50:06ZengMDPI AGCancers2072-66942021-03-01136118710.3390/cancers13061187Molecular Signature of Small Cell Lung Cancer after Treatment Failure: The <i>MCM</i> Complex as Therapeutic TargetShunsuke Misono0Keiko Mizuno1Takayuki Suetsugu2Kengo Tanigawa3Nijiro Nohata4Akifumi Uchida5Hiroki Sanada6Reona Okada7Shogo Moriya8Hiromasa Inoue9Naohiko Seki10Department of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, JapanDepartment of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, JapanDepartment of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, JapanDepartment of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, JapanMerck Sharp and Dohme (MSD) K.K., Tokyo 102-8667, JapanDepartment of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, JapanDepartment of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, JapanDepartment of Functional Genomics, Chiba University Graduate School of Medicine, Chuo-ku, Chiba 260-8670, JapanDepartment of Biochemistry and Genetics, Chiba University Graduate School of Medicine, Chuo-ku, Chiba 260-8670, JapanDepartment of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, JapanDepartment of Functional Genomics, Chiba University Graduate School of Medicine, Chuo-ku, Chiba 260-8670, JapanSmall cell lung cancer (SCLC) is a highly aggressive cancer, and patients who become refractory to first-line treatment have a poor prognosis. The development of effective treatment regimens is urgently needed. In this study, we identified a gene expression signature of SCLC after treatment failure using SCLC clinical specimens (GEO accession number: GSE162102). A total of 1,136 genes were significantly upregulated in SCLC tissues. These upregulated genes were subjected to KEGG pathway analysis, and “cell cycle”, “Fanconi anemia”, “alcoholism”, “systemic lupus erythematosus”, “oocyte meiosis”, “homologous recombination”, “DNA replication”, and “p53 signaling” were identified as the enriched pathways among the genes. We focused on the cell cycle pathway and investigated the clinical significance of four genes associated with this pathway: minichromosome maintenance (<i>MCM</i>) 2, <i>MCM4</i>, <i>MCM6</i>, and <i>MCM7</i>. The overexpression of these <i>MCM</i> genes was confirmed in SCLC clinical specimens. Knockdown assays using siRNAs targeting each of these four <i>MCM</i> genes showed significant attenuation of cancer cell proliferation. Moreover, siRNA-mediated knockdown of each <i>MCM</i> gene enhanced the cisplatin sensitivity of SCLC cells. Our SCLC molecular signature based on SCLC clinical specimens after treatment failure will provide useful information to identify novel molecular targets for this disease.https://www.mdpi.com/2072-6694/13/6/1187small cell lung cancercell cycle pathway<i>MCM2</i><i>MCM4</i><i>MCM6</i><i>MCM7</i> |
| spellingShingle | Shunsuke Misono Keiko Mizuno Takayuki Suetsugu Kengo Tanigawa Nijiro Nohata Akifumi Uchida Hiroki Sanada Reona Okada Shogo Moriya Hiromasa Inoue Naohiko Seki Molecular Signature of Small Cell Lung Cancer after Treatment Failure: The <i>MCM</i> Complex as Therapeutic Target Cancers small cell lung cancer cell cycle pathway <i>MCM2</i> <i>MCM4</i> <i>MCM6</i> <i>MCM7</i> |
| title | Molecular Signature of Small Cell Lung Cancer after Treatment Failure: The <i>MCM</i> Complex as Therapeutic Target |
| title_full | Molecular Signature of Small Cell Lung Cancer after Treatment Failure: The <i>MCM</i> Complex as Therapeutic Target |
| title_fullStr | Molecular Signature of Small Cell Lung Cancer after Treatment Failure: The <i>MCM</i> Complex as Therapeutic Target |
| title_full_unstemmed | Molecular Signature of Small Cell Lung Cancer after Treatment Failure: The <i>MCM</i> Complex as Therapeutic Target |
| title_short | Molecular Signature of Small Cell Lung Cancer after Treatment Failure: The <i>MCM</i> Complex as Therapeutic Target |
| title_sort | molecular signature of small cell lung cancer after treatment failure the i mcm i complex as therapeutic target |
| topic | small cell lung cancer cell cycle pathway <i>MCM2</i> <i>MCM4</i> <i>MCM6</i> <i>MCM7</i> |
| url | https://www.mdpi.com/2072-6694/13/6/1187 |
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