Affiliation:
1. Department of Stomatology Qingdao West Coast New District Central Hospital Qingdao China
2. Department of Stomatology, Qingdao Hospital University of Health and Rehabilitation Sciences (Qingdao Municipal Hospital) Qingdao China
3. Department of Oromaxillofacial Head and Neck Oncology, Shanghai Ninth People's Hospital, College of Stomatology Shanghai Jiao Tong University School of Medicine Shanghai China
Abstract
AbstractGeranylgeranyltransferase type I (GGTase‐I) significantly affects Rho proteins, such that the malignant progression of several cancers may be induced. Nevertheless, the effect and underlying mechanism of GGTase‐I in the malignant progression of salivary adenoid cystic carcinoma (SACC) remain unclear. This study primarily aimed to investigate the role and mechanism of GGTase‐I in mediating the malignant progression of SACC. The level of GGTase‐I gene in cells was stably knocked down by short hairpin RNA‐EGFP‐lentivirus. The effects of GGTase‐I silencing on the migration, invasion, and spread of cells were examined, the messenger RNA levels of GGTase‐I and RhoA genes of SACC cells after GGTase‐I knockdown were determined, and the protein levels of RhoA and RhoA membrane of SACC cells were analyzed. Moreover, the potential underlying mechanism of silencing GGTase‐I on the above‐mentioned aspects in SACC cells was assessed by examining the protein expression of ROCK1, MLC, p‐MLC, E‐cadherin, Vimentin, MMP2, and MMP9. Furthermore, the underlying mechanism of SACC cells proliferation was investigated through the analysis of the expression of cyclinD1, MYC, E2F1, and p21CIP1/WAF1. Besides, the change of RhoA level in SACC tissues compared with normal paracancer tissues was demonstrated through quantitative reverse‐transcription polymerase chain reaction and western blot experiments. Next, the effect after GGTase‐I silencing was assessed through the subcutaneous tumorigenicity assay. As indicated by the result of this study, the silencing of GGTase‐I significantly reduced the malignant progression of tumors in vivo while decreasing the migration, invasion, and proliferation of SACC cells and RhoA membrane, Vimentin, ROCK1, p‐MLC, MMP2, MMP9, MYC, E2F1, and CyclinD1 expression. However, the protein expression of E‐cadherin and p21CIP1/WAF1 was notably upregulated. Subsequently, no significant transform of RhoA and MLC proteins was identified. Furthermore, RhoA expression in SACC tissues was significantly higher than that in paracancerous tissues. As revealed by the results of this study, GGTase‐I shows a correlation with the proliferation of SACC through the regulation of cell cycle and may take on vital significance in the migration and invasion of SACC by regulating RhoA/ROCK1/MLC signaling pathway. GGTase‐I is expected to serve as a novel exploration site of SACC.
Subject
Cell Biology,General Medicine