Silencing of CPNE1-TRAF2 Axis Restrains the Development of Pancreatic Cancer.

BACKGROUND: Copine 1 (CPNE1) acts as a promoter in the progression of many kinds of cancers with the exception of pancreatic cancer (PC). This research is designed to probe the function of the CPNE1-tumor necrosis factor receptor-associated factor 2 (TRAF2) axis in PC. METHODS: In vivo and in vitro models of PC were constructed, and a series of biological function tests, including MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide], colony formation, flow cytometry, and immunohistochemistry, were performed. RESULTS: The level of CPNE1 elevated dramatically in PC cells. Downregulation of CPNE1in PC cells resulted in the inhibition of colony formation and proliferation. In addition, the silencing of CPNE1 induced the G1/S arrest and apoptosis in PC cells. Additionally, TRAF2 positively interacted with CPNE1 in PANC cells. CPNE1 silencing also inhibited the growth of tumors in in vivo mouse models. Functional experiments revealed that the anti-tumor effect of CPNE1 silencing was counteracted by TRAF2 overexpression, and the tumor-promoting effect of TRAF2 overexpression was reversed by CPNE1 silencing. CONCLUSIONS: In summary, our findings indicate that the silencing of the CPNE1-TRAF2 axis restrains PC development.

High expression of Plnc RNA-1 promotes the progression of colorectal cancer.

PURPOSE: To study the expression of Plnc RNA-1 in colorectal cancer tissues and cells, and to explore the role of Plnc RNA-1 in the regulation of cell cycle and in the progression of colorectal cancer. METHODS: A total of 77 cases of colorectal cancer tissues were retrospectively analyzed. Thirty colorectal normal tissues composed the control group. The expression of Plnc RNA-1 in colorectal cancer tissues at different stages was detected by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) so as to analyze the influence of Plnc RNA-1 on the survival of colorectal cancer patients and the accuracy of colorectal cancer diagnosis. Besides, SW116 and LOVO cell lines were transfected with si-Plnc RNA-1, pc-DNA-Plnc RNA-1 as well as their negative controls to achieve Plnc RNA-1 knockdown or overexpression. Then, we detected the transfection efficiency by qRT-PCR. Furthermore, cell counting kit-8 (CCK-8) and colony formation assays were performed to explore the effect of Plnc RNA-1 on colorectal cancer cells proliferation. Flow cytometry was used to examine the effect of Plnc RNA-1 on the cell cycle. In addition, western blotting was used to detect the expression levels of p-GSK3ß, p-Rb and CyclinD1. RESULTS: The expression level of Plnc RNA-1 in 77 colorectal cancer tissues was significantly higher than that of the control. Plnc RNA-1 expression level in patients with infiltrating T3+T4 stages was higher than that in infiltrating T1+T2 stages. In stages III+IV patients, the expression level of Plnc RNA-1 was higher than that of stages I+II. Plnc RNA-1 high expression group exhibited significantly lower survival rate than Plnc RNA-1 low expression group, suggesting there was a significant positive correlation between the sensitivity of colorectal cancer diagnosis and the expression of Plnc RNA-1. Overexpression of Plnc RNA-1 could significantly increase the viability and proliferation in the SW116 cells. In the LOVO cell line, knockdown of Plnc RNA-1 significantly decreased cell viability and proliferation. In the LOVO cell line, knockdown of Plnc RNA-1 promoted cell cycle and decreased the expression of cell cycle-related proteins p-GSK3ß, p-Rb and cyclinD1.In the SW116 cell line, overexpression of Plnc RNA-1 led to cell cycle arrest and increased the expression of cell cycle-related proteins. CONCLUSIONS: The expression of Plnc RNA-1 in colorectal cancer cells was significantly upregulated. Plnc RNA-1 participated in the development of colorectal cancer through regulating the cell cycle, which may provide a new theoretical basis for the treatment of colorectal cancer and a new therapeutic target.