Expression Of GNA14 In Endometrial Cancer And Its Role In The Proliferation And Apoptosis Of Endometrial Carcinoma Cell

Objective: Endometrial cancer is one of the most common malignant tumors in female reproductive tract.The overall prognosis of endometrial cancer is good,whereas the mortality is high in relapsed patients.Previous studies show that GNA14 plays an important role in the development and progress of gastric cancer and vascular tumors.However,there are no evidences demonstrating the role of GNA14 in endometrial cancer.Here,we explored the function of GNA14 in the development and progression of endometrial cancer and the related mechanism.Methods: Immunohistochemistry was performed to explore the expression of GNA14 in 88 cases of endometrial cancer tissue,22 cases of endometrial dysplasia tissue and 41 cases of endometrial simple hyperplasia tissue.GNA14 mRNA level in the endometrial cancer cell lines HEC-1-A and ishikawa was detected by Real-Time PCR.Lentivirus-mediated RNA interference was used to knockdown GNA14.The assays were performed to analyze the effect of GNA14 knockdown on proliferation,apoptosis and cell cycle of endometrial cancer cells.Finally,the effect of GNA14 knockdown on apoptosis related signaling pathway was detected by protein microarray.Results: The expression of GNA14 in endometrial atypical hyperplasia tissues was higher than that in endometrial simple hyperplasia tissues(p=0.018).Comparing with endometrial simple hyperplasia tissues,GNA14 expression was higher in endometrial carcinoma tissue(p<0.001),while there was no difference in endometrial cancer tissues and endometrial atypical tissues(p>0.05).GNA14 was highly expressed in the endometrial cancer cell lines HEC-1-A and ishikawa.GNA14 was efficiently knocked down in endometrial cancer cells.High content screening cell count and CCK8 assays indicated that GNA14 knockdown significantly inhibited the proliferation of endometrial cancer cells.Annexin V/APC staining and caspase-3/7 activity assay showed that knockdown of GNA14 induced the apoptosis of endometrial cancer cells.Flow cytometry results indicated that down-regulated GNA14 reduced the DNA synthesis of endometrial cancer cell lines and led to G2/M phase block of cell cycle,resulting in cell cycle disturbance.Furthermore,GNA14 knockdown markedly up-regulate the expression of Fas and caspase-3.Conclusion: Highly expressed GNA14 is correlated with the development and progression of endometrial cancer.Knockdown of GNA14 might inhibit the proliferation of endometrial cancer cells by activating the death receptor signaling pathway,suggesting that GNA14 acts as an oncogene.