872 - Comparative proteomic profiles of cervical cancer and paried paracancerous tissue and the potential effects of DUSP7 over-expression through inhibiting RAS pathway on the biological characteristics of human cervical cancer cell line SIHA

Background

The present study aimed to compare the protein profiles between paired samples of cervical cancer and paracancerous tissue and to identify a series of differentially expressed proteins (DEPs) through quantitative proteomics.

Methods

The DEPs were identified through proteomic profiles of three paired samples of cervical cancer (CC) and paracancerous tissue and through IHC examination in the CC tissue arrays. The lentiviral particles containing DUSP7 gene were transfected into SIHA cells (DUSP7-SIHA). CCK8 assay, colony formation assay, wound healing assay and transwell migration assay were used to evaluate the ability of cell proliferation, cell clone formation, cell migration and invasion. Immunofluorescence assay was used to detect the expression of E-cadherin and Vimentin in the target cells.

Results

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 >2cm and parametrial infiltration. The decreased expression of DUSP7, and increased expression of PLD1 were adversely related to patients’ relapse (P = 0.003, 0.040, and 0.001, respectively) and survival (P = 0.034, 0.001, and 0.006, respectively). The DUSP7-SIHA cells proliferated slower than NC-SIHA cells, based on a clear delay in the doubling time (47.72±1.14 h vs. 23.99±0.47 h, P = 0.0001). Cell cycle analysis indicated that the DUSP7-SIHA cells displayed a concomitant decrease in the percentage of cells in S phase (37.71±0.53% vs. 46.96±0.59%, P < 0.0001) and a significant increase in the percentage of cells in G0/G1 phase (52.50±3.49% vs. 44.04±0.71%, P = 0.0473) suggesting that inhibited proliferation of DUSP7-SIHA cells might be due to the inactivation of DNA synthesis. E-cadherin increased but Vimentin was reduced in DUSP7-SIHA cells, which demonstrated that overexpression of DUSP7 had a potential role in inhibiting EMT of SIHA cells.

Conclusions

The biological function of DUSP7 was possibly achieved through dephosphorylation of the ERK1/2 and inactivation of the RAS pathway.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Beijing Chaoyang Hospital.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.