Silencing of CD147 inhibits cell proliferation, migration, invasion, lipid metabolism dysregulation and promotes apoptosis in lung adenocarcinoma via blocking the Rap1 signaling pathway
Abstract Objective CD147 is an important glycoprotein that participates in the progression of diverse cancers. This study aims to explore the specific function of CD147 in lung adenocarcinoma (LUAD) and to reveal related downstream molecular mechanisms. Methods Followed by silencing of CD147, the vi...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-10-01
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| Series: | Respiratory Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12931-023-02532-0 |
| _version_ | 1797247047772930048 |
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| author | Ning Zhang Zhouzhong Liu Xuwang Lai Shubin Liu Yuli Wang |
| author_facet | Ning Zhang Zhouzhong Liu Xuwang Lai Shubin Liu Yuli Wang |
| author_sort | Ning Zhang |
| collection | DOAJ |
| description | Abstract Objective CD147 is an important glycoprotein that participates in the progression of diverse cancers. This study aims to explore the specific function of CD147 in lung adenocarcinoma (LUAD) and to reveal related downstream molecular mechanisms. Methods Followed by silencing of CD147, the viability, migration, invasion, and apoptosis of LUAD cells were measured by CCK8, wound healing, transwell assay, and flow cytometer, respectively. The expression of CD147 and two markers of lipid metabolism (FASN and ACOX1) were detected by qRT-PCR. A xenograft tumor model was constructed to investigate the function of CD147 in vivo. Then transcriptome sequencing was performed to explore the potential mechanisms. After measuring the expression of Rap1 and p-p38 MAPK/p38 MAPK by western blot, the changes of CD147 and lipid metabolism markers (FASN, ACOX1) was detected by Immunohistochemistry. Moreover, a Rap1 activator and a Rap1 inhibitor were applied for feedback functional experiments. Results CD147 was up-regulated in LUAD cells, and its silencing inhibited cell proliferation, migration, invasion, lipid metabolism dysregulation and promoted apoptosis, while overexpression of CD147 showed the opposite results. Silencing of CD147 also inhibited the growth of tumor xenografts in mice. Transcriptome sequencing revealed 834 up-regulated differentially expressed genes (DEGs) and 602 down-regulated DEGs. After functional enrichment, the Rap1 signaling pathway was selected as a potential target, which was then verified to be blocked by CD147 silencing. In addition, the treatment of Rap1 activator weakened the inhibiting effects of si-CD147 on the proliferation, migration, invasion, and lipid metabolism in LUAD cells, while the intervention of RAP1 inhibitor showed the opposite results. Conclusions Silencing of CD147 inhibited the proliferation, migration, invasion, lipid metabolism dysregulation and promoted apoptosis of LUAD cells through blocking the Rap1 signaling pathway. |
| first_indexed | 2024-03-10T17:09:40Z |
| format | Article |
| id | doaj.art-1ea277d73a5d4859a20d40cc013eee44 |
| institution | Directory Open Access Journal |
| issn | 1465-993X |
| language | English |
| last_indexed | 2024-04-24T19:52:29Z |
| publishDate | 2023-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Respiratory Research |
| spelling | doaj.art-1ea277d73a5d4859a20d40cc013eee442024-03-24T12:29:53ZengBMCRespiratory Research1465-993X2023-10-0124111210.1186/s12931-023-02532-0Silencing of CD147 inhibits cell proliferation, migration, invasion, lipid metabolism dysregulation and promotes apoptosis in lung adenocarcinoma via blocking the Rap1 signaling pathwayNing Zhang0Zhouzhong Liu1Xuwang Lai2Shubin Liu3Yuli Wang4Department of Gastroenterology, Ganzhou People’s Hospital, the Affiliated Ganzhou Hospital of Nanchang UniversityDepartment of Oncology, Ganzhou People’s Hospital, the Affiliated Ganzhou Hospital of Nanchang UniversityDepartment of Oncology, Ganzhou People’s Hospital, the Affiliated Ganzhou Hospital of Nanchang UniversityDepartment of Oncology, Ganzhou People’s Hospital, the Affiliated Ganzhou Hospital of Nanchang UniversityDepartment of Oncology, Ganzhou People’s Hospital, the Affiliated Ganzhou Hospital of Nanchang UniversityAbstract Objective CD147 is an important glycoprotein that participates in the progression of diverse cancers. This study aims to explore the specific function of CD147 in lung adenocarcinoma (LUAD) and to reveal related downstream molecular mechanisms. Methods Followed by silencing of CD147, the viability, migration, invasion, and apoptosis of LUAD cells were measured by CCK8, wound healing, transwell assay, and flow cytometer, respectively. The expression of CD147 and two markers of lipid metabolism (FASN and ACOX1) were detected by qRT-PCR. A xenograft tumor model was constructed to investigate the function of CD147 in vivo. Then transcriptome sequencing was performed to explore the potential mechanisms. After measuring the expression of Rap1 and p-p38 MAPK/p38 MAPK by western blot, the changes of CD147 and lipid metabolism markers (FASN, ACOX1) was detected by Immunohistochemistry. Moreover, a Rap1 activator and a Rap1 inhibitor were applied for feedback functional experiments. Results CD147 was up-regulated in LUAD cells, and its silencing inhibited cell proliferation, migration, invasion, lipid metabolism dysregulation and promoted apoptosis, while overexpression of CD147 showed the opposite results. Silencing of CD147 also inhibited the growth of tumor xenografts in mice. Transcriptome sequencing revealed 834 up-regulated differentially expressed genes (DEGs) and 602 down-regulated DEGs. After functional enrichment, the Rap1 signaling pathway was selected as a potential target, which was then verified to be blocked by CD147 silencing. In addition, the treatment of Rap1 activator weakened the inhibiting effects of si-CD147 on the proliferation, migration, invasion, and lipid metabolism in LUAD cells, while the intervention of RAP1 inhibitor showed the opposite results. Conclusions Silencing of CD147 inhibited the proliferation, migration, invasion, lipid metabolism dysregulation and promoted apoptosis of LUAD cells through blocking the Rap1 signaling pathway.https://doi.org/10.1186/s12931-023-02532-0Lung adenocarcinomaCD147Transcriptome sequencingLipid metabolismRap1 signaling pathway |
| spellingShingle | Ning Zhang Zhouzhong Liu Xuwang Lai Shubin Liu Yuli Wang Silencing of CD147 inhibits cell proliferation, migration, invasion, lipid metabolism dysregulation and promotes apoptosis in lung adenocarcinoma via blocking the Rap1 signaling pathway Respiratory Research Lung adenocarcinoma CD147 Transcriptome sequencing Lipid metabolism Rap1 signaling pathway |
| title | Silencing of CD147 inhibits cell proliferation, migration, invasion, lipid metabolism dysregulation and promotes apoptosis in lung adenocarcinoma via blocking the Rap1 signaling pathway |
| title_full | Silencing of CD147 inhibits cell proliferation, migration, invasion, lipid metabolism dysregulation and promotes apoptosis in lung adenocarcinoma via blocking the Rap1 signaling pathway |
| title_fullStr | Silencing of CD147 inhibits cell proliferation, migration, invasion, lipid metabolism dysregulation and promotes apoptosis in lung adenocarcinoma via blocking the Rap1 signaling pathway |
| title_full_unstemmed | Silencing of CD147 inhibits cell proliferation, migration, invasion, lipid metabolism dysregulation and promotes apoptosis in lung adenocarcinoma via blocking the Rap1 signaling pathway |
| title_short | Silencing of CD147 inhibits cell proliferation, migration, invasion, lipid metabolism dysregulation and promotes apoptosis in lung adenocarcinoma via blocking the Rap1 signaling pathway |
| title_sort | silencing of cd147 inhibits cell proliferation migration invasion lipid metabolism dysregulation and promotes apoptosis in lung adenocarcinoma via blocking the rap1 signaling pathway |
| topic | Lung adenocarcinoma CD147 Transcriptome sequencing Lipid metabolism Rap1 signaling pathway |
| url | https://doi.org/10.1186/s12931-023-02532-0 |
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