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© The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Objective

Recent studies indicated that transmembrane protein 40 (TMEM40) is associated with several types of cancers but is not clear in cervical cancer (CC). The study aimed to examine the role of TMEM40 in CC and related mechanisms.

Methods

The expression of TMEM40 in CC tissues and cell lines was studied with western blot and real-time quantitative RT-PCR. The effect of TMEM40 on proliferation was evaluated by CCK-8, EdU and colony formation assay. The migration, invasion, cell cycle and apoptosis of CC cells were studied with wound healing, transwell assays and flow cytometry. Tumor growth was evaluated in vivo using a xenogenous subcutaneously implant model.

Results

The results revealed that the TMEM40 elevation in CC tissues and cell lines was closely correlated with tumor size and lymph node metastasis in clinical patients. Upregulation of TMEM40 with OE-TMEM40 vector promoted the invasion, migration and proliferation, inhibited the apoptosis and led to distinct S cell cycle arrest in CC cell lines. Silencing TMEM40 with shRNA inhibited the invasion, migration and proliferation, promoted apoptosis and led to a G0/G1 cell cycle arrest in CC cell lines. Silence of TMEM40 downregulated the expression of c-MYC, Cyclin D1, matrix metalloproteinase-1 (MMP-1) and matrix metalloproteinase-9 (MMP-9), but in contrast, activated p53 and several apoptosis related proteins such as p53, Caspase-3, Caspase-9 and PARP1. In addition, TMEM40 silencing dramatically decreased tumor growth in mice models.

Conclusion

The present study demonstrates that TMEM40 upregulation can be a potential prognostic biomarker and contribute to CC development.

Details

Title
Upregulation of TMEM40 is associated with the malignant behavior and promotes tumor progression in cervical cancer
Author
Zhang, Zhen-Fei 1 ; Liu, Fang 2 ; Zhang, Han-Rong 3 ; Liu, Bing 2 ; Zheng, Shu-Qian 2 ; Ye, Wan-Qian 2 ; Ding, Jia-Nan 2 ; Zhou, Ze-Jie 4 ; Luo, Hui-Xian 4 ; Wu, Fang 4 ; Guo, Xuan-Min 5 ; Zhou, Jue-Yu 2 ; Guo, Yong-Hui 4 

 Zhujiang Hospital, Southern Medical University, Department of Laboratory Medicine, Guangzhou, People’s Republic of China (GRID:grid.417404.2) (ISNI:0000 0004 1771 3058); Southern Medical University, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Guangzhou, People’s Republic of China (GRID:grid.284723.8) (ISNI:0000 0000 8877 7471) 
 Southern Medical University, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Guangzhou, People’s Republic of China (GRID:grid.284723.8) (ISNI:0000 0000 8877 7471) 
 Nanfang College-Guangzhou, Department of Nursing and Health, Guangzhou, People’s Republic of China (GRID:grid.284723.8) 
 Zhujiang Hospital, Southern Medical University, Department of Laboratory Medicine, Guangzhou, People’s Republic of China (GRID:grid.417404.2) (ISNI:0000 0004 1771 3058) 
 Zhujiang Hospital, Southern Medical University, Department of Urology, Guangzhou, People’s Republic of China (GRID:grid.417404.2) (ISNI:0000 0004 1771 3058) 
Pages
43
Publication year
2023
Publication date
Dec 2023
Publisher
Springer Nature B.V.
e-ISSN
27306011
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2800406722
Copyright
© The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.