TPX2 gene silencing inhibits cell proliferation and promotes apoptosis through negative regulation of AKT signaling pathway in ovarian cancer.

Ovarian cancer (OC) is the leading cause of death from gynecological malignancy. Accumulated studies have revealed that targeting protein for Xklp2 (TPX2) was tightly associated with the development and progression of OC. The present study further determined a novel mechanism of TPX2 in OC via the AKT signaling pathway. The differentially expressed genes were screened in GEO database for gene expression microarray of OC. Bioinformatics was used to analyze the key differentially expressed genes in OC. We prepared CD133/1+ OC stem cells. Then cells were treated with TPX2-1 siRNA and perifcsine to explore the correlation of TPX2 and the AKT signaling pathway. We determined the expression of TPX2, AKT, Pl3 K, PTEN, caspase-3, Bax and Bcl-2 in OC cells. Cell proliferation, migration, invasion, and apoptosis rate were respectively measured using MTT and EdU assays, Transwell assay, Scratch test, and flow cytometry. Xenograft tumor in nude mice was used to determine the effect of TPX2 in OC cells in vitro. Initially, TPX2 overexpression was observed in OC, and TPX2 mediated the effect of the AKT signaling pathway in OC. TPX2 knockdown decreased expression of AKT, Pl3 K, and Bcl-2, and the extent of AKT phosphorylation, but increased expression of PTEN, Caspase-3, and Bax. Furthermore, TPX2 knockdown suppressed OC cell proliferation, migration and invasion, but promoted OC cell apoptosis. Taken together, TPX2 silencing negatively regulates the AKT signaling pathway by which OC cell proliferation was inhibited yet cell apoptosis was accelerated, suggesting a potential therapeutic approach to OC.

Upregulation of DAPK2 ameliorates oxidative damage and apoptosis of placental cells in hypertensive disorder complicating pregnancy by suppressing human placental microvascular endothelial cell autophagy through the mTOR signaling pathway.

Death-associated protein kinase 2 (DAPK2) has indicated functional roles in cellular processes, including survival, apoptosis, and autophagy. This study is aimed to identify the effect of DAPK2 on oxidative damage and apoptosis of placental cells in hypertensive disorder complicating pregnancy (HDCP) through mTOR pathway. Microarray-based gene expression analysis was performed to predict the differentially expressed genes related to HDCP. To investigate the specific mechanism of DAPK2 in HDCP cells, placental microvascular endothelial cells were treated with mimic or siRNA of DAPK2 and mTOR to detect the expression of related genes, cell autophagy and apoptosis and oxidative damage. Finally, rats were modeled with HDCP to verify the cell experiment results. DAPK2 was downregulated in HDCP, and could activate mTOR. Besides, DAPK2 overexpression led to decreases in autophagy in HPVECs as well as apoptosis and oxidative damage in placental cells indicated by a substantial decrease in Beclin-1, LC3 II/LC3 I and Bax along with an increase in Bcl-2, 4EBP1 and p70S6K. It also ameliorates blood pressure elevation in HDCP rats. The study defined remission effect of DAPK2 on placental cell oxidative damage and apoptosis in HDCP via mTOR activation. Together, DAPK2 regulating mTOR pathway presents a promising therapy for HDCP treatment.