Research On The Novel Tumor Suppressor Gene DTWD1in Gastric Cancer

Background:Gastric cancer (GC), a serious threat to human health, is one of the most common malignant tumors but also the second leading cause of cancer-related death worldwide. In recent years, epigenetic regulatory role in the occurrence and development of tumors has aroused increasing concern. Our research team has revealed that DTWD1may play a suppression role in gastric cancer, its transcription factor is P53and its expression was suppressed by HDAC3. However, the evidence revealing that DTWD1plays a suppression role in gastric cancer is not sufficient. What is more, mechanisms of the tumor suppressor gene DTWD1in gastric cancer is still unclear.Objective:At present, it has been determined that DTWD1may be a potential tumor suppressor gene regulated by P53, and its expression was suppressed by HDAC3in our laboratory. However, the biological function and specific mechanism of DTWD1has not been fully determined. We attempt to explore the biological function and regulation mechanism of DTWD1through a series of in vitro and in vivo experiments. In this study, it has been further confirmed that DTWD1functioned as a tumor suppressor by downregulating cyclin B1expression to inhibit proliferation.Methods:To further determine the long-term effect of DTWD1on gastric cancer cells, we engineered SGC7901cells to stably express DTWD1in a doxycycline-dependent manner and constructed stable DTWD1cell line. We observed the effect of exogenous DTWD1on the cell phenotype through manual counting. Then we established nude mice model to further verify the effects of DTWD1in cancer cell growth in vivo. In addition, we used Western Blot, flow cytometry testing cell cycle and apoptosis, immunohistochemistry, special Senescence Detection Kit to elucidate the mechanism of DTWD1inhibiting the occurrence and development of tumor.Results:In this study, we further confirmed that DTWD1functioned as a tumor suppressor in gastric cancer and exerted its biological function by arresting the cell cycle through downregulating cyclin B1expression. In vivo and in vitro experiments proved that DTWD1could effectively inhibit tumor cell growth. However, DTWDl showed no significant influence on apoptosis, autophagy, senescence, cell cycle and PTEN-PI3K-AKT, mTOR signal pathway of gastric cancer cells. The mechanism of DTWD1functioned as a tumor suppressor needs further detected.Conclusion:DTWD1functioned as a tumor suppressor in gastric cancer and exerted its biological function by arresting the cell cycle through downregulating cyclin B1expression.Innovation points:1DTWD1is a novel tumor suppressor in human gastric cancer. 2DTWD1acts as an important part to inhibit cancer cells growth by arresting the cell cycle in the G2/M phase.