The protective role of DMBT1 in cervical squamous cell carcinoma

Abstract

To explore the possible influence of deleted in malignant brain tumor 1 (DMBT1) in cervical squamous cell carcinoma (CSCC). DMBT1 expression was detected by Real-time reverse transcription PCR (qRT-PCR) and immunohistochemistry in CSCC and adjacent normal tissues from 167 CSCC patients, and its relationship with clinicopathological features and prognosis was analyzed. Besides, the in vitro experiments, including MTT, Cell-Light EdU, Wound-healing, Transwell invasion, Annexin V-FITC/PI staining, qRT-PCR, and Western blot, were performed in SiHa and CaSKi cells, which were both divided into Blank, Vector, and DMBT1 groups. The mRNA level and the positive expression rate of DMBT1 in CSCC tissues were lower than the adjacent normal tissues. Moreover, DMBT1 positive rate was linked to FIGO stage, tumor diameter, lymph node metastasis, and tumor differentiation of CSCC. Besides, patients with positive DMBT1 expression had higher 5-year survival rate than those negative ones. According to the in vitro experiments, SiHa and CaSKi cells with overexpressed DMBT1 showed the inhibition of proliferative ability and the enhancement of apoptosis with the upregulated pro-apoptosis proteins (Bax and Cleaved caspase-3) and down-regulated anti-apoptosis protein Bcl-2. Moreover, compared with Blank group, DMBT1 group presented decrease in the migration and invasion of SiHa and CaSKi cells with the down-expression of interstitial markers (N-cadherin and Vimentin) and the up-expression of epithelial marker E-cadherin. DMBT1 was decreased in CSCC, whereas its overexpression can not only inhibit the proliferation, migration, and invasion, but induce the apoptosis of human CSCC cells, being a novel strategy for CSCC treatment.

Keywords: DMBT1; EMT; apoptosis; cervical squamous cell carcinoma; proliferation.