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In this study, we explored the effects of treating human endometrial cancer cells with γ-synuclein-specific short hairpin RNA (shRNA) and elucidated the associated mechanisms in vitro and in vivo through the p38, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK) signaling pathways. Cell proliferation and migration were assessed using CCK8, Transwell, and scratch wound healing assays. Flow cytometry and laser scanning confocal microscopy were used to detect cell cycle changes. Relative levels of phosphorylated and non-phosphorylated (p) p38, ERK1/2 and JNK1/2/3 were determined in vitro and in vivo using simple western blotting assays. Cell proliferation in the experimental group decreased significantly and cells transfected with shRNA showed reduced migration rates (P < 0.05). p-p38, p-ERK1/2, and p-JNK1/2/3 levels were downregulated in the experimental group in vitro and in vivo. Tumor volumes and weights in the experimental group were significantly lower (P < 0.05). Tumor formation time in the negative control group was significantly shorter (P < 0.05). Flow cytometry showed that the number of cells in the G1 and mitotic phases increased and that in the S phase decreased after SNCG silencing (P < 0.05). Confocal microscopy showed that the percentage of cells in the mitotic phase increased after SNCG gene silencing (P < 0.05). We conclude that shRNA-mediated suppression of γ-synuclein decreased the proliferation, migration, and tumorigenicity of endometrial cancer cells via downregulation of p38, ERK, and JNK phosphorylation. High SNCG expression is closely related to the growth cycle of endometrial cancer cells.

PARP10 is an intracellular mono-ADP ribosyltransferase and recent reports suggest that it regulates proliferation of some cell types. However, its effect on the proliferation of colorectal carcinoma cells has not yet been systematically reported. We explored the influence of PARP10 on the proliferation of several colorectal carcinoma cell types and carried out initial studies on the underlying mechanisms. Inhibition of the enzymatic activity of PARP10 led to significantly decreases in proliferative ability in LoVo cells and CT26 cells in vitro and suppressed growth of CT26 tumours in the subaxilliary region in Balb/c mice in vivo. Cell-cycle arrest accompanied these observations. Expression of the nuclear transfer factor β-catenin and it trans-location to the nucleus were also affected and the expression of its associated signal proteins Axin2 and c-Myb were increased and decreased, respectively. We demonstrate that PARP10 promotes proliferation of those colorectal carcinoma cells which express significant levels of PARP10. This promotion is suppressed when the enzymatic activity is inhibited. β-Catenin is likely to be the mediator of the antiproliferative effect.

Deregulated expression of proteins involved in the SUMOylation pathway has been detected in several tumors. SUMO1-activating enzyme subunit 1 (SAE1) plays an important role in this process. We found that SAE1 was highly expressed in the colon cancer cell line RKO and used lentivirus-mediated siRNA to suppress SAE1 expressionin RKO cells. RNA-interference efficiently and specifically downregulated the target gene expression in RKO on both mRNA and protein levels. Silencing of SAE1 inhibited proliferation and reduced colony formation of RKO cells. Furthermore, as it has been shown by flow cytometry analysis, specific knockdown of SAE1 slowed down the cell population at G0/G1 phase and induced apoptosis of RKO cells. On the base of results obtained, one can suppose the biological significance of SAE1 in colon tumorigenesis and a use of this protein as a novel molecular target for colon cancer therapy.