Desumoylating Isopeptidase 2 (DESI2) Inhibits Proliferation and Promotes Apoptosis of Pancreatic Cancer Cells through Regulating PI3K/AKT/mTOR Signaling Pathway

摘要

This study aimed to investigate the effects of desumoylating isopeptidase 2 (DESI2) on tumor cell proliferation, apoptosis and invasion of pancreatic cancer, and to assess the signaling pathway involved. Overexpression and silence of DESI2 were designed and the experiments were divided into 5 groups: a normal control group, an interference control group (shRNA-NC); an interference group (sh-DESI2); an overexpression control group (NC), an overexpression group (DESI2). Quantitative real time polymerase chain reaction (qRT-PCR) was used to screen the appropriate interference sequence. The silencing and overexpression of DESI2 were confirmed by qRT-PCR and western blotting. Cell cycling, apoptosis, invasion, and the expression of phosphatidylinositol-3-kinase (PI3K)-protein kinase B (AKT)-mammalian target of rapamycin (mTOR) pathway and caspase 3 were measured. Overexpression and silence of DESI2 were successfully designed in two pancreatic cancer cells, and the interference effect of sh-DESI2-3 showed the best silencing effects. The biological activities of DESI2 were detected in both ASPC-1 and PANCE-1 cells. Our results showed that cell proliferation was significantly increased in the sh-DESI2 group, while decreased in DESI2 group compared with the control group in both cell lines. In ASPC-1 cells, the events in G1 phase decreased and in S phase increased obviously in the sh-DESI2 group, compared with control group. An opposite result was found when DESI2 was overexpressed. In PANCE-1 cells, the events in G2 phase were higher in the sh-DESI2 group, while in the DESI2 group was significantly lower than that in control group. In ASPC-1 and PANCE-1 cells, sh-DESI2 group showed decreased apoptosis, increased cell invasion and increased expression of AKT, p-Akt, PI3K, p-PI3K, p-mTOR and mTOR and decreased caspase 3 expression compared with the control group, while overexpression of DESI2 leaded to increased apoptosis, decreased cell invasion and reduced expression of AKT, p-Akt, PI3K, p-PI3K, p-mTOR and mTOR and increased expression of caspase 3. DESI2 regulates the proliferation and apoptosis of pancreatic cancer cells through PI3K/AKT/mTOR signaling pathway.