Selenium‐binding protein 1 inhibits malignant progression and induces apoptosis via distinct mechanisms in non‐small cell lung cancer
Abstract Background Selenium is an essential trace element in the human body. In epidemiological and clinical studies, Se supplementation significantly reduced the incidence of lung cancer in individuals with low baseline Se levels. The significant action of selenium is based on the selenium‐contain...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-08-01
|
| Series: | Cancer Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cam4.6309 |
| _version_ | 1827307664534667264 |
|---|---|
| author | Ying Zhu Qiang Pu Qiongyin Zhang Yang Liu Yongfang Ma Yue Yuan Lunxu Liu Wen Zhu |
| author_facet | Ying Zhu Qiang Pu Qiongyin Zhang Yang Liu Yongfang Ma Yue Yuan Lunxu Liu Wen Zhu |
| author_sort | Ying Zhu |
| collection | DOAJ |
| description | Abstract Background Selenium is an essential trace element in the human body. In epidemiological and clinical studies, Se supplementation significantly reduced the incidence of lung cancer in individuals with low baseline Se levels. The significant action of selenium is based on the selenium‐containing protein as a mediator. Of note, the previous studies reported that the expression of selenium‐binding protein 1 (SELENBP1) was obviously decreased in many human cancer tissues including non‐small cell lung cancer (NSCLC). However, its roles in the origin and development of NSCLC are still unclear. Methods The expression of SELENBP1 was measured by qRT‐PCR, Western blotting and IHC in our collected clinical NSCLC tissues and cell lines. Next, the CCK‐8, colony formation, wound‐haeling, Millicell, Transwell, FCM assay, and in vivo xenograft model were performed to explore the function of SELENBP1 in NSCLC. The molecular mechanisms of SELENBP1 were investigated by Western blotting or IF assay. Results We further identified that the expression of SELENBP1 was significantly decreased in NSCLC tissues in TCGA database and 45 out of 59 collected clinical NSCLC tissues compared with adjacent nontumor tissues, as well as in four NSCLC cell lines compared with normal lung cells. Particularly, we unexpectedly discovered that SELENBP1 was obviously expressed in alveolar type 2 (AT‐II) cells for the first time. Then, a series of in vitro experiments uncovered that overexpression of SELENBP1 inhibited the proliferation, migration, and invasion of NSCLC cells, and induced cell apoptosis. Moreover, overexpression of SELENBP1 also inhibited growth and induced apoptosis of NSCLC cells in vivo. Mechanistically, we demonstrated that overexpression of SELENBP1 inhibited the malignant characteristics of NSCLC cells in part via inactivating the PI3K/AKT/mTOR signal pathway. Meanwhile, we found that overexpression of SELENBP1 inducing the apoptosis of NSCLC cells was associated with the activation of caspase‐3 signaling pathway under nonhigh level of oxidative stress, but overexpression of SELENBP1 facilitating the cell apoptosis might be related to its combining with GPX1 and colocalizing in the nucleus under high level of oxidative stress. Conclusions Our findings highlighted that SELENBP1 was an important tumor suppressor during the origin and development of NSCLC. It may help to discover novel biomarkers or drug therapy targets for NSCLC. |
| first_indexed | 2024-03-12T00:55:23Z |
| format | Article |
| id | doaj.art-a4431151e7264c11b0ebfe7a783cd2b7 |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-04-24T18:43:24Z |
| publishDate | 2023-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-a4431151e7264c11b0ebfe7a783cd2b72024-03-27T09:11:00ZengWileyCancer Medicine2045-76342023-08-011216171491717010.1002/cam4.6309Selenium‐binding protein 1 inhibits malignant progression and induces apoptosis via distinct mechanisms in non‐small cell lung cancerYing Zhu0Qiang Pu1Qiongyin Zhang2Yang Liu3Yongfang Ma4Yue Yuan5Lunxu Liu6Wen Zhu7State Key Laboratory of Biotherapy and Cancer Center West China Hospital, Sichuan University Chengdu Sichuan ChinaDepartment of Thoracic Surgery Institute of Thoracic Oncology, West China Hospital, Sichuan University Chengdu Sichuan ChinaState Key Laboratory of Biotherapy and Cancer Center West China Hospital, Sichuan University Chengdu Sichuan ChinaState Key Laboratory of Biotherapy and Cancer Center West China Hospital, Sichuan University Chengdu Sichuan ChinaState Key Laboratory of Biotherapy and Cancer Center West China Hospital, Sichuan University Chengdu Sichuan ChinaState Key Laboratory of Biotherapy and Cancer Center West China Hospital, Sichuan University Chengdu Sichuan ChinaDepartment of Thoracic Surgery Institute of Thoracic Oncology, West China Hospital, Sichuan University Chengdu Sichuan ChinaState Key Laboratory of Biotherapy and Cancer Center West China Hospital, Sichuan University Chengdu Sichuan ChinaAbstract Background Selenium is an essential trace element in the human body. In epidemiological and clinical studies, Se supplementation significantly reduced the incidence of lung cancer in individuals with low baseline Se levels. The significant action of selenium is based on the selenium‐containing protein as a mediator. Of note, the previous studies reported that the expression of selenium‐binding protein 1 (SELENBP1) was obviously decreased in many human cancer tissues including non‐small cell lung cancer (NSCLC). However, its roles in the origin and development of NSCLC are still unclear. Methods The expression of SELENBP1 was measured by qRT‐PCR, Western blotting and IHC in our collected clinical NSCLC tissues and cell lines. Next, the CCK‐8, colony formation, wound‐haeling, Millicell, Transwell, FCM assay, and in vivo xenograft model were performed to explore the function of SELENBP1 in NSCLC. The molecular mechanisms of SELENBP1 were investigated by Western blotting or IF assay. Results We further identified that the expression of SELENBP1 was significantly decreased in NSCLC tissues in TCGA database and 45 out of 59 collected clinical NSCLC tissues compared with adjacent nontumor tissues, as well as in four NSCLC cell lines compared with normal lung cells. Particularly, we unexpectedly discovered that SELENBP1 was obviously expressed in alveolar type 2 (AT‐II) cells for the first time. Then, a series of in vitro experiments uncovered that overexpression of SELENBP1 inhibited the proliferation, migration, and invasion of NSCLC cells, and induced cell apoptosis. Moreover, overexpression of SELENBP1 also inhibited growth and induced apoptosis of NSCLC cells in vivo. Mechanistically, we demonstrated that overexpression of SELENBP1 inhibited the malignant characteristics of NSCLC cells in part via inactivating the PI3K/AKT/mTOR signal pathway. Meanwhile, we found that overexpression of SELENBP1 inducing the apoptosis of NSCLC cells was associated with the activation of caspase‐3 signaling pathway under nonhigh level of oxidative stress, but overexpression of SELENBP1 facilitating the cell apoptosis might be related to its combining with GPX1 and colocalizing in the nucleus under high level of oxidative stress. Conclusions Our findings highlighted that SELENBP1 was an important tumor suppressor during the origin and development of NSCLC. It may help to discover novel biomarkers or drug therapy targets for NSCLC.https://doi.org/10.1002/cam4.6309caspase‐3 pathwayGPX1NSCLCPI3K/AKT/mTOR pathwaySELENBP1tumor suppressor |
| spellingShingle | Ying Zhu Qiang Pu Qiongyin Zhang Yang Liu Yongfang Ma Yue Yuan Lunxu Liu Wen Zhu Selenium‐binding protein 1 inhibits malignant progression and induces apoptosis via distinct mechanisms in non‐small cell lung cancer Cancer Medicine caspase‐3 pathway GPX1 NSCLC PI3K/AKT/mTOR pathway SELENBP1 tumor suppressor |
| title | Selenium‐binding protein 1 inhibits malignant progression and induces apoptosis via distinct mechanisms in non‐small cell lung cancer |
| title_full | Selenium‐binding protein 1 inhibits malignant progression and induces apoptosis via distinct mechanisms in non‐small cell lung cancer |
| title_fullStr | Selenium‐binding protein 1 inhibits malignant progression and induces apoptosis via distinct mechanisms in non‐small cell lung cancer |
| title_full_unstemmed | Selenium‐binding protein 1 inhibits malignant progression and induces apoptosis via distinct mechanisms in non‐small cell lung cancer |
| title_short | Selenium‐binding protein 1 inhibits malignant progression and induces apoptosis via distinct mechanisms in non‐small cell lung cancer |
| title_sort | selenium binding protein 1 inhibits malignant progression and induces apoptosis via distinct mechanisms in non small cell lung cancer |
| topic | caspase‐3 pathway GPX1 NSCLC PI3K/AKT/mTOR pathway SELENBP1 tumor suppressor |
| url | https://doi.org/10.1002/cam4.6309 |
| work_keys_str_mv | AT yingzhu seleniumbindingprotein1inhibitsmalignantprogressionandinducesapoptosisviadistinctmechanismsinnonsmallcelllungcancer AT qiangpu seleniumbindingprotein1inhibitsmalignantprogressionandinducesapoptosisviadistinctmechanismsinnonsmallcelllungcancer AT qiongyinzhang seleniumbindingprotein1inhibitsmalignantprogressionandinducesapoptosisviadistinctmechanismsinnonsmallcelllungcancer AT yangliu seleniumbindingprotein1inhibitsmalignantprogressionandinducesapoptosisviadistinctmechanismsinnonsmallcelllungcancer AT yongfangma seleniumbindingprotein1inhibitsmalignantprogressionandinducesapoptosisviadistinctmechanismsinnonsmallcelllungcancer AT yueyuan seleniumbindingprotein1inhibitsmalignantprogressionandinducesapoptosisviadistinctmechanismsinnonsmallcelllungcancer AT lunxuliu seleniumbindingprotein1inhibitsmalignantprogressionandinducesapoptosisviadistinctmechanismsinnonsmallcelllungcancer AT wenzhu seleniumbindingprotein1inhibitsmalignantprogressionandinducesapoptosisviadistinctmechanismsinnonsmallcelllungcancer |