The role and function of secretory protein MMP3 in cervical cancer

Abstract

Abstract OBJECTIVE Cervical cancer(CCA) is the second commonest malignancy among female all over the world, and present clinical treatments cannot solve the problems of high metastasis and chemotherapy-resistant in CCA. This study starts with RNA-seq analysis and aims to investigate the possibility of secretory protein MMP3 as a new diagnosis and therapeutic target in CCA. METHODS Through conjoint analysis of gene expression data as well as survival rate data, we explored the potential secretary proteins associated with CCA carcinogenesis and advance and verify the expression changes in serum of clinical patients. We knockdown or overexpress the secretory proteins then explore its influence on biological function of CCA cells. Cell viabilities and apoptosis levels are detected using CCK-8 kit and TUNEL staining assay respectively, the expression of apoptosis related proteins was verified by western blot. RESULTS By cross-analysis of The Cancer Genome Atlas (TCGA) database and MetazSecKB database, MMP3 gene was most significantly upregulated in CCA patients. Also, MMP3 protein was remarkably increased in the serum of clinical CCA patients and decreased after receiving treatment. Overexpression of MMP3 in HT-3 cells or culturing new cells using the supernatant of the medium after MMP3 overexpression could increase cell viability (p < 0.05) as well as proliferation (p < 0.05). What’s more, knockdown of MMP3 reduced the phosphorylation of PI3K as well as AKT proteins, while the PI3K phosphorylation inhibitors could suppress the impact of MMP3 on increasing cell proliferation as well as viability. Conclusion The secreted protein MMP3 is significantly related to the development and progression of CCA in clinical, and MMP3 can inhibit apoptosis of CCA cells through regulating PI3K/Akt signal pathway. Therefore, this study suggests that MMP3 could be an underlying target for early diagnosis, together wo and treatment of CCA in the future.