Silencing PROK2 Inhibits Invasion of Human Cervical Cancer Cells by Targeting MMP15 Expression

• Published in: International journal of molecular sciences 2020-09, Vol.21 (17), p.6391
• Main Authors: Wu, Min-Hua, Wu, Pei-Ru, Hsieh, Yi-Hsien, Lin, Chia-Liang, Liu, Chung-Jung, Ying, Tsung-Ho
• Format: Article
• Language: English
• Subjects: Apoptosis; Biomarkers; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Breast cancer; Cancer therapies; Cell adhesion & migration; Cell Cycle; Cell growth; Cell Movement; Cell Proliferation; Cervical cancer; Cervix; Chemotherapy; Colorectal cancer; Female; Gastrointestinal Hormones - antagonists & inhibitors; Gastrointestinal Hormones - genetics; Gastrointestinal Hormones - metabolism; Gene Expression Regulation, Neoplastic; Human papillomavirus; Humans; invasion; Liver cancer; Matrix Metalloproteinase 15 - chemistry; Matrix Metalloproteinase 15 - genetics; Matrix Metalloproteinase 15 - metabolism; Medical prognosis; Metastasis; migration; MMP15; Neoplasm Invasiveness; Neuroblastoma; Neuropeptides - antagonists & inhibitors; Neuropeptides - genetics; Neuropeptides - metabolism; Prognosis; PROK2; Prostate; Protein expression; Proteins; Radiation therapy; Survival; Tumor Cells, Cultured; Tumors; Uterine Cervical Neoplasms - genetics; Uterine Cervical Neoplasms - metabolism; Uterine Cervical Neoplasms - pathology; Womens health
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21176391

Cervical cancer is the second most frequent type of gynecologic cancer worldwide. Prokineticin 2 (PROK2) is reported to be involved in tumor progression in some malignant tumors. However, the role of PROK2 in the development of cervical cancer remains unknown. Our results indicate that PROK2 is overexpressed in the human cervical cancer. Cervical cancer patients with high PROK2 expression have a shorter overall survival rate (OS) and disease-free survival rate (DFS). PROK2 acts as a potential biomarker for predicting OS and DFS of cervical cancer patients. We further show that PROK2 is important factor for oncogenic migration and invasion in human cervical cancer cells. Knockdown PROK2 significantly inhibited cell migration, invasion, and MMP15 protein expression in HeLa cells. High expression of MMP15 is confirmed in the human cervical cancer, is significantly associated with the shorter overall survival rate (OS) and is correlated with PROK2 expression. Overexpression of PROK2 using PROK2 plasmid significantly reverses the function of knockdown PROK2, and further upregulates MMP15 expression, migration and invasion of human cervical cancer cells. In conclusion, our findings are the first to demonstrate the role of PROK2 as a novel and potential biomarker for clinical use, and reveal the oncogenic functions of PROK2 as therapeutic target for cervical cancer.