Schlafen 12 Is Prognostically Favorable and Reduces C-Myc and Proliferation in Lung Adenocarcinoma but Not in Lung Squamous Cell Carcinoma
Schlafen 12 (SLFN12) is an intermediate human Schlafen that induces differentiation in enterocytes, prostate, and breast cancer. We hypothesized that SLFN12 influences lung cancer biology. We investigated survival differences in high versus low SLFN12-expressing tumors in two databases. We then aden...
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| Format: | Article |
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MDPI AG
2020-09-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/10/2738 |
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| author | Sarmad Al-Marsoummi Jonathan Pacella Kaylee Dockter Matthew Soderberg Sandeep K. Singhal Emilie E. Vomhof-DeKrey Marc D. Basson |
| author_facet | Sarmad Al-Marsoummi Jonathan Pacella Kaylee Dockter Matthew Soderberg Sandeep K. Singhal Emilie E. Vomhof-DeKrey Marc D. Basson |
| author_sort | Sarmad Al-Marsoummi |
| collection | DOAJ |
| description | Schlafen 12 (SLFN12) is an intermediate human Schlafen that induces differentiation in enterocytes, prostate, and breast cancer. We hypothesized that SLFN12 influences lung cancer biology. We investigated survival differences in high versus low SLFN12-expressing tumors in two databases. We then adenovirally overexpressed SLFN12 (AdSLFN12) in HCC827, H23, and H1975 cells to model lung adenocarcinoma (LUAD), and in H2170 and HTB-182 cells representing lung squamous cell carcinoma (LUSC). We analyzed proliferation using a colorimetric assay, mRNA expression by RT-qPCR, and protein by Western blot. To further explore the functional relevance of SLFN12, we correlated SLFN12 with seventeen functional oncogenic gene signatures in human tumors. Low tumoral SLFN12 expression predicted worse survival in LUAD patients, but not in LUSC. AdSLFN12 modulated expression of SCGB1A1, SFTPC, HOPX, CK-5, CDH1, and P63 in a complex fashion in these cells. AdSLFN12 reduced proliferation in all LUAD cell lines, but not in LUSC cells. SLFN12 expression inversely correlated with expression of a myc-associated gene signature in LUAD, but not LUSC tumors. SLFN12 overexpression reduced c-myc protein in LUAD cell lines but not in LUSC, by inhibiting c-myc translation. Our results suggest SLFN12 improves prognosis in LUAD in part via a c-myc-dependent slowing of proliferation. |
| first_indexed | 2024-03-10T16:05:58Z |
| format | Article |
| id | doaj.art-bcbd5c7957b04568a081b50a675179f1 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T16:05:58Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-bcbd5c7957b04568a081b50a675179f12023-11-20T14:53:11ZengMDPI AGCancers2072-66942020-09-011210273810.3390/cancers12102738Schlafen 12 Is Prognostically Favorable and Reduces C-Myc and Proliferation in Lung Adenocarcinoma but Not in Lung Squamous Cell CarcinomaSarmad Al-Marsoummi0Jonathan Pacella1Kaylee Dockter2Matthew Soderberg3Sandeep K. Singhal4Emilie E. Vomhof-DeKrey5Marc D. Basson6Department of Biomedical Sciences, School of Medicine and the Health Sciences, University of North Dakota, Grand Forks, ND 58202, USADepartment of Biomedical Sciences, School of Medicine and the Health Sciences, University of North Dakota, Grand Forks, ND 58202, USADepartment of Biomedical Sciences, School of Medicine and the Health Sciences, University of North Dakota, Grand Forks, ND 58202, USADepartment of Biomedical Sciences, School of Medicine and the Health Sciences, University of North Dakota, Grand Forks, ND 58202, USADepartment of Pathology, School of Medicine and the Health Sciences, University of North Dakota, Grand Forks, ND 58202, USADepartment of Biomedical Sciences, School of Medicine and the Health Sciences, University of North Dakota, Grand Forks, ND 58202, USADepartment of Biomedical Sciences, School of Medicine and the Health Sciences, University of North Dakota, Grand Forks, ND 58202, USASchlafen 12 (SLFN12) is an intermediate human Schlafen that induces differentiation in enterocytes, prostate, and breast cancer. We hypothesized that SLFN12 influences lung cancer biology. We investigated survival differences in high versus low SLFN12-expressing tumors in two databases. We then adenovirally overexpressed SLFN12 (AdSLFN12) in HCC827, H23, and H1975 cells to model lung adenocarcinoma (LUAD), and in H2170 and HTB-182 cells representing lung squamous cell carcinoma (LUSC). We analyzed proliferation using a colorimetric assay, mRNA expression by RT-qPCR, and protein by Western blot. To further explore the functional relevance of SLFN12, we correlated SLFN12 with seventeen functional oncogenic gene signatures in human tumors. Low tumoral SLFN12 expression predicted worse survival in LUAD patients, but not in LUSC. AdSLFN12 modulated expression of SCGB1A1, SFTPC, HOPX, CK-5, CDH1, and P63 in a complex fashion in these cells. AdSLFN12 reduced proliferation in all LUAD cell lines, but not in LUSC cells. SLFN12 expression inversely correlated with expression of a myc-associated gene signature in LUAD, but not LUSC tumors. SLFN12 overexpression reduced c-myc protein in LUAD cell lines but not in LUSC, by inhibiting c-myc translation. Our results suggest SLFN12 improves prognosis in LUAD in part via a c-myc-dependent slowing of proliferation.https://www.mdpi.com/2072-6694/12/10/2738Schlafen 12c-myclung adenocarcinomalung squamous cell carcinomanon-small cell lung cancer |
| spellingShingle | Sarmad Al-Marsoummi Jonathan Pacella Kaylee Dockter Matthew Soderberg Sandeep K. Singhal Emilie E. Vomhof-DeKrey Marc D. Basson Schlafen 12 Is Prognostically Favorable and Reduces C-Myc and Proliferation in Lung Adenocarcinoma but Not in Lung Squamous Cell Carcinoma Cancers Schlafen 12 c-myc lung adenocarcinoma lung squamous cell carcinoma non-small cell lung cancer |
| title | Schlafen 12 Is Prognostically Favorable and Reduces C-Myc and Proliferation in Lung Adenocarcinoma but Not in Lung Squamous Cell Carcinoma |
| title_full | Schlafen 12 Is Prognostically Favorable and Reduces C-Myc and Proliferation in Lung Adenocarcinoma but Not in Lung Squamous Cell Carcinoma |
| title_fullStr | Schlafen 12 Is Prognostically Favorable and Reduces C-Myc and Proliferation in Lung Adenocarcinoma but Not in Lung Squamous Cell Carcinoma |
| title_full_unstemmed | Schlafen 12 Is Prognostically Favorable and Reduces C-Myc and Proliferation in Lung Adenocarcinoma but Not in Lung Squamous Cell Carcinoma |
| title_short | Schlafen 12 Is Prognostically Favorable and Reduces C-Myc and Proliferation in Lung Adenocarcinoma but Not in Lung Squamous Cell Carcinoma |
| title_sort | schlafen 12 is prognostically favorable and reduces c myc and proliferation in lung adenocarcinoma but not in lung squamous cell carcinoma |
| topic | Schlafen 12 c-myc lung adenocarcinoma lung squamous cell carcinoma non-small cell lung cancer |
| url | https://www.mdpi.com/2072-6694/12/10/2738 |
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