TIM-1 promotes proliferation and metastasis, and inhibits apoptosis, in cervical cancer through the PI3K/AKT/p53 pathway
Abstract Background T-cell immunoglobulin mucin-1 (TIM-1) has been reported to be associated with the biological behavior of several malignant tumors; however, it is not clear whether it has a role in cervical cancer (CC). Methods TIM-1 expression in cervical epithelial tumor tissues and cells was d...
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| Format: | Article |
| Language: | English |
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BMC
2022-04-01
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| Series: | BMC Cancer |
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| Online Access: | https://doi.org/10.1186/s12885-022-09386-7 |
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| author | Liuyan Chen Jilin Qing Yangyang Xiao Xiaomei Huang Yanlin Chi Zhizhong Chen |
| author_facet | Liuyan Chen Jilin Qing Yangyang Xiao Xiaomei Huang Yanlin Chi Zhizhong Chen |
| author_sort | Liuyan Chen |
| collection | DOAJ |
| description | Abstract Background T-cell immunoglobulin mucin-1 (TIM-1) has been reported to be associated with the biological behavior of several malignant tumors; however, it is not clear whether it has a role in cervical cancer (CC). Methods TIM-1 expression in cervical epithelial tumor tissues and cells was detected by immunohistochemistry or real-time quantitative-PCR and western blotting. CC cells from cell lines expressing low levels of TIM-1 were infected with lentiviral vectors encoding TIM-1. Changes in the malignant behavior of CC cells were assessed by CCK-8, wound healing, Transwell migration and invasion assays, and flow cytometry in vitro; while a xenograft tumor model was established to analyze the effects of TIM-1 on tumor growth in vivo. Changes in the levels of proteins related to the cell cycle, apoptosis, and Epithelial-mesenchymal transition (EMT) were determined by western blotting. Results TIM-1 expression was higher in CC tissues, than in high grade squamous intraepithelial lesion, low grade squamous intraepithelial lesion, or normal cervical tissues, and was also expressed in three CC cell lines. In HeLa and SiHa cells overexpressing TIM-1, proliferation, invasion, and migration increased, while whereas apoptosis was inhibited. Furthermore, TIM-1 downregulated the expression of p53, BAX, and E-cadherin, and increased cyclin D1, Bcl-2, Snail1, N-cadherin, vimentin, MMP-2, and VEGF. PI3K, p-AKT, and mTOR protein levels also increased, while total AKT protein levels remained unchanged. Conclusions Our study indicated that TIM-1 overexpression promoted cell migration and invasion, and inhibited cell apoptosis in CC through modulation of the PI3K/AKT/p53 and PI3K/AKT/mTOR signaling pathways, and may be a candidate diagnostic biomarker of this disease. |
| first_indexed | 2024-04-12T22:44:18Z |
| format | Article |
| id | doaj.art-f3b0b76152c240fb8755b79e05d6866e |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-12T22:44:18Z |
| publishDate | 2022-04-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-f3b0b76152c240fb8755b79e05d6866e2022-12-22T03:13:37ZengBMCBMC Cancer1471-24072022-04-0122111710.1186/s12885-022-09386-7TIM-1 promotes proliferation and metastasis, and inhibits apoptosis, in cervical cancer through the PI3K/AKT/p53 pathwayLiuyan Chen0Jilin Qing1Yangyang Xiao2Xiaomei Huang3Yanlin Chi4Zhizhong Chen5Joint Inspection Center of Precision Medicine, The People’s Hospital of Guangxi Zhuang Autonomous Region & Guangxi Academy of Medical SciencesCenter for Reproductive Medicine and Genetics, The People’s Hospital of Guangxi Zhuang Autonomous Region & Guangxi Academy of Medical SciencesDepartment of Clinical Laboratory, Binzhou Medical University HospitalJoint Inspection Center of Precision Medicine, The People’s Hospital of Guangxi Zhuang Autonomous Region & Guangxi Academy of Medical SciencesDepartment of Clinical Laboratory, the first affiliated hospital of Guangxi University of Chinese MedicineJoint Inspection Center of Precision Medicine, The People’s Hospital of Guangxi Zhuang Autonomous Region & Guangxi Academy of Medical SciencesAbstract Background T-cell immunoglobulin mucin-1 (TIM-1) has been reported to be associated with the biological behavior of several malignant tumors; however, it is not clear whether it has a role in cervical cancer (CC). Methods TIM-1 expression in cervical epithelial tumor tissues and cells was detected by immunohistochemistry or real-time quantitative-PCR and western blotting. CC cells from cell lines expressing low levels of TIM-1 were infected with lentiviral vectors encoding TIM-1. Changes in the malignant behavior of CC cells were assessed by CCK-8, wound healing, Transwell migration and invasion assays, and flow cytometry in vitro; while a xenograft tumor model was established to analyze the effects of TIM-1 on tumor growth in vivo. Changes in the levels of proteins related to the cell cycle, apoptosis, and Epithelial-mesenchymal transition (EMT) were determined by western blotting. Results TIM-1 expression was higher in CC tissues, than in high grade squamous intraepithelial lesion, low grade squamous intraepithelial lesion, or normal cervical tissues, and was also expressed in three CC cell lines. In HeLa and SiHa cells overexpressing TIM-1, proliferation, invasion, and migration increased, while whereas apoptosis was inhibited. Furthermore, TIM-1 downregulated the expression of p53, BAX, and E-cadherin, and increased cyclin D1, Bcl-2, Snail1, N-cadherin, vimentin, MMP-2, and VEGF. PI3K, p-AKT, and mTOR protein levels also increased, while total AKT protein levels remained unchanged. Conclusions Our study indicated that TIM-1 overexpression promoted cell migration and invasion, and inhibited cell apoptosis in CC through modulation of the PI3K/AKT/p53 and PI3K/AKT/mTOR signaling pathways, and may be a candidate diagnostic biomarker of this disease.https://doi.org/10.1186/s12885-022-09386-7T-cell immunoglobulin mucin-1ApoptosisInvasionMetastasisEMTCervical cancer |
| spellingShingle | Liuyan Chen Jilin Qing Yangyang Xiao Xiaomei Huang Yanlin Chi Zhizhong Chen TIM-1 promotes proliferation and metastasis, and inhibits apoptosis, in cervical cancer through the PI3K/AKT/p53 pathway BMC Cancer T-cell immunoglobulin mucin-1 Apoptosis Invasion Metastasis EMT Cervical cancer |
| title | TIM-1 promotes proliferation and metastasis, and inhibits apoptosis, in cervical cancer through the PI3K/AKT/p53 pathway |
| title_full | TIM-1 promotes proliferation and metastasis, and inhibits apoptosis, in cervical cancer through the PI3K/AKT/p53 pathway |
| title_fullStr | TIM-1 promotes proliferation and metastasis, and inhibits apoptosis, in cervical cancer through the PI3K/AKT/p53 pathway |
| title_full_unstemmed | TIM-1 promotes proliferation and metastasis, and inhibits apoptosis, in cervical cancer through the PI3K/AKT/p53 pathway |
| title_short | TIM-1 promotes proliferation and metastasis, and inhibits apoptosis, in cervical cancer through the PI3K/AKT/p53 pathway |
| title_sort | tim 1 promotes proliferation and metastasis and inhibits apoptosis in cervical cancer through the pi3k akt p53 pathway |
| topic | T-cell immunoglobulin mucin-1 Apoptosis Invasion Metastasis EMT Cervical cancer |
| url | https://doi.org/10.1186/s12885-022-09386-7 |
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