SNCG gene silencing in gallbladder cancer cells inhibits key tumorigenic activities

Abstract

We recently determined that synuclein-gamma (SNCG) is highly expressed in human gallbladder cancer (GBC), and its abnormal expression is associated with tumor aggressiveness. To investigate the effects of SNCG gene silencing on the tumorigenic profiles of the GBC cell line, NOZ, short-hairpin RNA (shRNA) interference was employed. Specifically, the SNCG transcript was targeted by SNCG-shRNA lentiviral particles designed to silence SNCG gene expression. Following selection of NOZ cells stably expressing SNCG-shRNA, SNCG expression was examined by western blot and semi-quantitative RT-PCR analyses. Phenotypic hallmarks of gallbladder carcinogenesis were assayed by CCK-8, soft agar (colony formation), modified Boyden-Chamber (invasion), and flow cytometry (cell-cycle and apoptosis) assays. Our results showed that SNCG gene silencing in NOZ cells inhibited cell growth, colony formation, and invasion. In addition, it directly increased the effectiveness of paclitaxel in inducing G2/M cell-cycle arrest and cell apoptosis. Data from our in vivo study showed a decrease in tumor growth and weight in mice injected with SNCG-silenced NOZ cells. Together, these findings suggest that SNCG plays an important role in the progression of GBC.

siRNA Targeting of the <b><i>SNCG</i></b> Gene Inhibits the Growth of Gastric Carcinoma SGC7901 Cells in vitro and in vivo<b> </b>by Downregulating the Phosphorylation of AKT/ERK

“…diversified cancer types, including gastric cancer, but rarely expressed in tumor-matched non-neoplastic adjacent tissues (0.6%) [Shi et al, 2011;Liu et al, 2016]. These findings suggest that knockdown of SNCG expression may be an effective therapy in several cancer types [Morgan et al, 2009;Han et al, 2012]. However, studies examining the correlation of SNCG expression with gastric cancer biological effects in vitro and in vivo are missing or are limited only to the meta-analysis of gene and tissue expression profiles in gastric cancer.…”

The breast cancer susceptibility gene product (γ-synuclein) alters cell behavior through it interaction with phospholipase Cβ

“…Aberrant overexpression of γ-synuclein has been observed in various pathological conditions especially in a variety of cancers including prostate, colorectal, pancreatic, ovarian and gall bladder [5, 6]. Surprisingly, γ-synuclein was first discovered in 1996 in breast cancers and was named the Breast Cancer Susceptibility Gene Product, but was later identified as being a member of the neuronal synuclein family [7].…”

“…Studies have shown that knockdown of γ-synuclein expression in prostate [5] and gall bladder [6] cancer cells greatly reduced the occurrence of cancerous phenotypes such as cell proliferation, migration, invasion and cell cycle arrest. Further studies have shown that downregulation of γ-synuclein expression in MCF7 cells (an early-stage breast cancer cell line) resulted in a drastic reduction in cell migration and proliferation [11], as well as the propensity to form tumors when xenografted into mice [12].…”

Molecular biology of gallbladder cancer: Potential clinical implications

“…Many other molecular markers, proteins and factors, including PIK3CA,[52], methylation,[5354] protein gene product 9.5,[55] proteomics,[56] Raf-1,[57] RASSF1A,[58] Reg IV,[59] Rsf-1,[60] Survivin,[61] Syndecan-1,[62] Synuclein-gamma,[63] TAG-72,[64] Telomeres,[65] Telomerase activity (hTERT),[66] TEM8,[67] Thrombospondin,[68] Thymidine phosphorylase,[69] Angiogenesis,[70] TNF-alpha,[71] TLRs,[72] Topoisomerase,[73] Vasculogenic mimicry,[74] VEGFs,[75–77] and XPC[78] are involved in the development or progress of GBC. Some of these directly exert an effect on clinical outcome, while some link with development or of GBC.…”