DUSP7 inhibits cervical cancer progression by inactivating the RAS pathway.

Huimin Bai,Meiying Song,Mulan Jin,Ruili Jiao,Weihua Li,Haiteng Deng,Meizhu Xiao,Zhengyu Zhang,Jing Zhao

doi:10.1111/jcmm.16865

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.

Highlights

Human cervical carcinoma (CC) ranks as the third most common cancer worldwide and is the most frequent gynecological cancer in developing countries
Western Blot and IHC staining analyses confirmed the results from quantitative proteomic analysis showing that HRAS, P-ERK1/2, and PLD1 levels were increased whereas DUSP7 level was decreased in CC tissue compared with the paired normal paracancerous tissues
The IHC results from the CC Tissue microarray (TMA) analysis showed that the decreased expression of DUSP7 (P = 0.045 and 0.044, respectively) and increased expression of PLD1 (P = 0.046 and 0.028, respectively) were significantly associated with a tumor size > 2 cm and parametrial infiltration

Summary

Introduction

Human cervical carcinoma (CC) ranks as the third most common cancer worldwide and is the most frequent gynecological cancer in developing countries. The incidence and mortality of CC are on the rise. The key etiologic role of human papillomavirus (HPV) in the development of CC and its precursors has been well documented convincingly [2], and the use of HPV vaccination in women has the potential to reduce the incidence of CC reduced in the future. Due to the high price of the vaccine, coverage rates are still low, especially in low- or middle-income countries [3]. Viral presence is not sufficient to induce CC [4], suggesting that a distinct molecular mechanism could play a key role in its transformation and progression

Methods

Results

Conclusion