Impact of <i>TMPRSS2</i> Expression, Mutation Prognostics, and Small Molecule (CD, AD, TQ, and TQFL12) Inhibition on Pan-Cancer Tumors and Susceptibility to SARS-CoV-2
As a cellular protease, transmembrane serine protease 2 (TMPRSS2) plays roles in various physiological and pathological processes, including cancer and viral entry, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Herein, we conducted expression, mutation, and prognostic analyse...
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| Format: | Article |
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MDPI AG
2022-11-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/21/7413 |
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| author | Jiewen Fu Shuguang Liu Qi Tan Zhiying Liu Jie Qian Ting Li Jiaman Du Binghui Song Dabing Li Lianmei Zhang Jiayue He Kan Guo Baixu Zhou Hanchun Chen Shangyi Fu Xiaoyan Liu Jingliang Cheng Tao He Junjiang Fu |
| author_facet | Jiewen Fu Shuguang Liu Qi Tan Zhiying Liu Jie Qian Ting Li Jiaman Du Binghui Song Dabing Li Lianmei Zhang Jiayue He Kan Guo Baixu Zhou Hanchun Chen Shangyi Fu Xiaoyan Liu Jingliang Cheng Tao He Junjiang Fu |
| author_sort | Jiewen Fu |
| collection | DOAJ |
| description | As a cellular protease, transmembrane serine protease 2 (TMPRSS2) plays roles in various physiological and pathological processes, including cancer and viral entry, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Herein, we conducted expression, mutation, and prognostic analyses for the <i>TMPRSS2</i> gene in pan-cancers as well as in COVID-19-infected lung tissues. The results indicate that TMPRSS2 expression was highest in prostate cancer. A high expression of TMPRSS2 was significantly associated with a short overall survival in breast invasive carcinoma (BRCA), sarcoma (SARC), and uveal melanoma (UVM), while a low expression of TMPRSS2 was significantly associated with a short overall survival in lung adenocarcinoma (LUAD), demonstrating TMPRSS2 roles in cancer patient susceptibility and severity. Additionally, TMPRSS2 expression in COVID-19-infected lung tissues was significantly reduced compared to healthy lung tissues, indicating that a low TMPRSS2 expression may result in COVID-19 severity and death. Importantly, TMPRSS2 mutation frequency was significantly higher in prostate adenocarcinoma (PRAD), and the mutant TMPRSS2 pan-cancer group was significantly associated with long overall, progression-free, disease-specific, and disease-free survival rates compared to the wild-type (WT) TMPRSS2 pan-cancer group, demonstrating loss of functional roles due to mutation. Cancer cell lines were treated with small molecules, including cordycepin (CD), adenosine (AD), thymoquinone (TQ), and TQFL12, to mediate TMPRSS2 expression. Notably, CD, AD, TQ, and TQFL12 inhibited TMPRSS2 expression in cancer cell lines, including the PC3 prostate cancer cell line, implying a therapeutic role for preventing COVID-19 in cancer patients. Together, these findings are the first to demonstrate that small molecules, such as CD, AD, TQ, and TQFL12, inhibit TMPRSS2 expression, providing novel therapeutic strategies for preventing COVID-19 and cancers. |
| first_indexed | 2024-03-09T18:48:26Z |
| format | Article |
| id | doaj.art-e7c4f8f2c1744c519136d316c4f21eb1 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T18:48:26Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-e7c4f8f2c1744c519136d316c4f21eb12023-11-24T06:03:48ZengMDPI AGMolecules1420-30492022-11-012721741310.3390/molecules27217413Impact of <i>TMPRSS2</i> Expression, Mutation Prognostics, and Small Molecule (CD, AD, TQ, and TQFL12) Inhibition on Pan-Cancer Tumors and Susceptibility to SARS-CoV-2Jiewen Fu0Shuguang Liu1Qi Tan2Zhiying Liu3Jie Qian4Ting Li5Jiaman Du6Binghui Song7Dabing Li8Lianmei Zhang9Jiayue He10Kan Guo11Baixu Zhou12Hanchun Chen13Shangyi Fu14Xiaoyan Liu15Jingliang Cheng16Tao He17Junjiang Fu18Key Laboratory of Epigenetics and Oncology, the Research Center for Preclinical Medicine, Southwest Medical University, Luzhou 646000, ChinaKey Laboratory of Epigenetics and Oncology, the Research Center for Preclinical Medicine, Southwest Medical University, Luzhou 646000, ChinaKey Laboratory of Epigenetics and Oncology, the Research Center for Preclinical Medicine, Southwest Medical University, Luzhou 646000, ChinaKey Laboratory of Epigenetics and Oncology, the Research Center for Preclinical Medicine, Southwest Medical University, Luzhou 646000, ChinaKey Laboratory of Epigenetics and Oncology, the Research Center for Preclinical Medicine, Southwest Medical University, Luzhou 646000, ChinaKey Laboratory of Epigenetics and Oncology, the Research Center for Preclinical Medicine, Southwest Medical University, Luzhou 646000, ChinaKey Laboratory of Epigenetics and Oncology, the Research Center for Preclinical Medicine, Southwest Medical University, Luzhou 646000, ChinaKey Laboratory of Epigenetics and Oncology, the Research Center for Preclinical Medicine, Southwest Medical University, Luzhou 646000, ChinaKey Laboratory of Epigenetics and Oncology, the Research Center for Preclinical Medicine, Southwest Medical University, Luzhou 646000, ChinaDepartment of Pathology, The Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical University, Huai’an 223300, ChinaKey Laboratory of Epigenetics and Oncology, the Research Center for Preclinical Medicine, Southwest Medical University, Luzhou 646000, ChinaKey Laboratory of Epigenetics and Oncology, the Research Center for Preclinical Medicine, Southwest Medical University, Luzhou 646000, ChinaKey Laboratory of Epigenetics and Oncology, the Research Center for Preclinical Medicine, Southwest Medical University, Luzhou 646000, ChinaDepartment of Biochemistry, School of Life Sciences, Central South University, Changsha 410013, ChinaSchool of Medicine, Baylor College of Medicine, Houston, TX 77030, USAKey Laboratory of Epigenetics and Oncology, the Research Center for Preclinical Medicine, Southwest Medical University, Luzhou 646000, ChinaKey Laboratory of Epigenetics and Oncology, the Research Center for Preclinical Medicine, Southwest Medical University, Luzhou 646000, ChinaKey Laboratory of Epigenetics and Oncology, the Research Center for Preclinical Medicine, Southwest Medical University, Luzhou 646000, ChinaKey Laboratory of Epigenetics and Oncology, the Research Center for Preclinical Medicine, Southwest Medical University, Luzhou 646000, ChinaAs a cellular protease, transmembrane serine protease 2 (TMPRSS2) plays roles in various physiological and pathological processes, including cancer and viral entry, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Herein, we conducted expression, mutation, and prognostic analyses for the <i>TMPRSS2</i> gene in pan-cancers as well as in COVID-19-infected lung tissues. The results indicate that TMPRSS2 expression was highest in prostate cancer. A high expression of TMPRSS2 was significantly associated with a short overall survival in breast invasive carcinoma (BRCA), sarcoma (SARC), and uveal melanoma (UVM), while a low expression of TMPRSS2 was significantly associated with a short overall survival in lung adenocarcinoma (LUAD), demonstrating TMPRSS2 roles in cancer patient susceptibility and severity. Additionally, TMPRSS2 expression in COVID-19-infected lung tissues was significantly reduced compared to healthy lung tissues, indicating that a low TMPRSS2 expression may result in COVID-19 severity and death. Importantly, TMPRSS2 mutation frequency was significantly higher in prostate adenocarcinoma (PRAD), and the mutant TMPRSS2 pan-cancer group was significantly associated with long overall, progression-free, disease-specific, and disease-free survival rates compared to the wild-type (WT) TMPRSS2 pan-cancer group, demonstrating loss of functional roles due to mutation. Cancer cell lines were treated with small molecules, including cordycepin (CD), adenosine (AD), thymoquinone (TQ), and TQFL12, to mediate TMPRSS2 expression. Notably, CD, AD, TQ, and TQFL12 inhibited TMPRSS2 expression in cancer cell lines, including the PC3 prostate cancer cell line, implying a therapeutic role for preventing COVID-19 in cancer patients. Together, these findings are the first to demonstrate that small molecules, such as CD, AD, TQ, and TQFL12, inhibit TMPRSS2 expression, providing novel therapeutic strategies for preventing COVID-19 and cancers.https://www.mdpi.com/1420-3049/27/21/7413<i>TMPRSS2</i> geneSARS-CoV-2prostate adenocarcinomasusceptibilitycordycepin (CD)adenosine (AD) |
| spellingShingle | Jiewen Fu Shuguang Liu Qi Tan Zhiying Liu Jie Qian Ting Li Jiaman Du Binghui Song Dabing Li Lianmei Zhang Jiayue He Kan Guo Baixu Zhou Hanchun Chen Shangyi Fu Xiaoyan Liu Jingliang Cheng Tao He Junjiang Fu Impact of <i>TMPRSS2</i> Expression, Mutation Prognostics, and Small Molecule (CD, AD, TQ, and TQFL12) Inhibition on Pan-Cancer Tumors and Susceptibility to SARS-CoV-2 Molecules <i>TMPRSS2</i> gene SARS-CoV-2 prostate adenocarcinoma susceptibility cordycepin (CD) adenosine (AD) |
| title | Impact of <i>TMPRSS2</i> Expression, Mutation Prognostics, and Small Molecule (CD, AD, TQ, and TQFL12) Inhibition on Pan-Cancer Tumors and Susceptibility to SARS-CoV-2 |
| title_full | Impact of <i>TMPRSS2</i> Expression, Mutation Prognostics, and Small Molecule (CD, AD, TQ, and TQFL12) Inhibition on Pan-Cancer Tumors and Susceptibility to SARS-CoV-2 |
| title_fullStr | Impact of <i>TMPRSS2</i> Expression, Mutation Prognostics, and Small Molecule (CD, AD, TQ, and TQFL12) Inhibition on Pan-Cancer Tumors and Susceptibility to SARS-CoV-2 |
| title_full_unstemmed | Impact of <i>TMPRSS2</i> Expression, Mutation Prognostics, and Small Molecule (CD, AD, TQ, and TQFL12) Inhibition on Pan-Cancer Tumors and Susceptibility to SARS-CoV-2 |
| title_short | Impact of <i>TMPRSS2</i> Expression, Mutation Prognostics, and Small Molecule (CD, AD, TQ, and TQFL12) Inhibition on Pan-Cancer Tumors and Susceptibility to SARS-CoV-2 |
| title_sort | impact of i tmprss2 i expression mutation prognostics and small molecule cd ad tq and tqfl12 inhibition on pan cancer tumors and susceptibility to sars cov 2 |
| topic | <i>TMPRSS2</i> gene SARS-CoV-2 prostate adenocarcinoma susceptibility cordycepin (CD) adenosine (AD) |
| url | https://www.mdpi.com/1420-3049/27/21/7413 |
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