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DUSP7 inhibits cervical cancer progression by inactivating the RAS pathway |
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| Authors: | Huimin Bai Meiying Song Ruili Jiao Weihua Li Jing Zhao Meizhu Xiao Mulan Jin Zhengyu Zhang Haiteng Deng |
| Institution: | 1. Department of Obstetrics and Gynecology, Beijing Chao-yang Hospital, Capital Medical University, Beijing, China;2. Department of Obstetrics and Gynecology, Beijing Chao-yang Hospital, Capital Medical University, Beijing, China
Department of Obstetrics and Gynecology, Fuxing Hospital, Capital Medical University, Beijing, China Contribution: Conceptualization (lead), Data curation (lead), Formal analysis (lead), Investigation (lead), Methodology (lead), Project administration (lead), Supervision (lead), Visualization (lead), Writing - review & editing (lead);3. Department of Obstetrics and Gynecology, Beijing Chaoyang District Maternal and Child Health Care Hospital, Beijing, China Contribution: Conceptualization (equal), Data curation (equal), Investigation (equal), Software (equal), Validation (equal), Visualization (equal);4. Department of Obstetrics and Gynecology, Beijing Chao-yang Hospital, Capital Medical University, Beijing, China Contribution: Funding acquisition (equal), Investigation (equal), Methodology (equal), Software (equal);5. Department of Obstetrics and Gynecology, Beijing Chao-yang Hospital, Capital Medical University, Beijing, China Contribution: Methodology (equal), Project administration (equal), Software (equal), Validation (equal);6. Department of Obstetrics and Gynecology, Beijing Chao-yang Hospital, Capital Medical University, Beijing, China Contribution: Data curation (equal), Funding acquisition (equal), Investigation (equal), Methodology (equal), Validation (equal);7. Department of Pathology, Beijing Chao-yang Hospital, Capital Medical University, Beijing, China Contribution: Formal analysis (equal), Investigation (equal), Methodology (equal), Project administration (equal), Software (equal);8. Department of Obstetrics and Gynecology, Beijing Chao-yang Hospital, Capital Medical University, Beijing, China Contribution: Conceptualization (lead), Data curation (lead), Formal analysis (lead), Investigation (lead), Supervision (lead), Visualization (lead), Writing - original draft (lead), Writing - review & editing (lead);9. MOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University, Beijing, China |
| Abstract: | To determine the differentially expressed proteins (DEPs) between paired samples of cervical cancer (CC) and paracancerous tissue by quantitative proteomics and to examine the effects of DUSP7 expression on the tumorigenesis and progression of CC. Proteomic profiles of three paired samples of CC and paracancerous tissue were quantitatively analysed to identify DEPs. The relationship between DEP expression and patient clinicopathological characteristics and prognosis was evaluated. The effects of the selected DEPs on CC progression were examined in SIHA cells. A total of 129 DEPs were found. Western blot and immunohistochemistry (IHC) staining analyses confirmed the results from quantitative proteomic analysis showing that the selected DEP, HRAS, P-ERK1/2, and PLD1 levels were increased, whereas the DUSP7 level was decreased in CC tissue compared with the paired normal paracancerous tissues. The IHC results from the CC TMA analysis showed that the decreased expression of DUSP7 (p = 0.045 and 0.044) was significantly associated with a tumour size >2 cm and parametrial infiltration. In addition, the decreased expression of DUSP7 and increased expression of p-ERK1/2 were adversely related to patient relapse (p = 0.003 and 0.001) and survival (p = 0.034 and 0.006). The expression of HRAS and p-ERK1/2 was decreased in DUSP7-SIHA cells compared with NC-SIHA cells (p = 0.0003 and 0.0026). Biological functions in vitro, including invasion, migration and proliferation and tumour formation in vivo were decreased in DUSP7-SIHA cells (all p < 0.05) but increased in shDUSP7-SIHA cells (all p < 0.05). DUSP7 inhibits cervical cancer progression by inactivating the RAS pathway. |
| Keywords: | biological characteristics cervical cancer DUSP7 lentiviral vector proteomics RAS pathway |