CDCA3 is a potential prognostic marker that promotes cell proliferation in gastric cancer

Abstract

Gastric cancer (GC) is an aggressive and highly lethal gastrointestinal cancer, with an exceedingly poor prognosis. In the present study, the carcinogenic mechanism of human GC and the role of cell division cycle-associated 3 (CDCA3) were investigated. The expression levels of CDCA3 were investigated in GC samples and matched, peritumoral tissues by reverse transcription-quantitative polymerase chain reaction and immunohistochemical analysis. The effects of CDCA3 on cell proliferation were explored by Cell Counting Kit-8, colony formation, flow cytometric analysis and western blotting in vitro, and in vivo tumorigenesis in nude mice. The results demonstrated that CDCA3 expression was increased in human GC tissues compared with those in adjacent non-tumor tissues. Evaluation of the clinicopathological significance indicated that CDCA3 was closely associated with features of GC and patients with unfavorable overall survival times. CDCA3 overexpression resulted in the stimulation of cell growth and colony formation in vitro and xenograft tumors in vivo. Conversely, knockdown of CDCA3 inhibited these effects. Furthermore, the ectopic expression of CDCA3 in SGC7901 cells consistently promoted the cell cycle transition from the G 0 /G 1 phase to the S phase; whereas knockdown of CDCA3 in BGC823 cells blocked the transition from the G 0 /G 1 phase. Additionally, the present study revealed that the Ras signaling pathway was involved in CDCA3-mediated regulation of GC cell proliferation. CDCA3 activated the Ras signaling pathway to promote cell proliferation in vitro and in vivo in GC cells. Levels of CDCA3 greatly accelerated the progression of human GC. CDCA3 served as an oncogene, and may be a significant prognostic predictor and a novel therapeutic target for patients with GC.

Downregulation of CDCA3 expression inhibits tumor formation in pancreatic cancer

“…knockdown reversed those effects [35]. Additionally, related studied showed the expression of CDCA3 was significantly increased in hepatocellular carcinoma [19] and prostate cancer [20].…”

CircUBE2D2 (hsa_circ_0005728) promotes cell proliferation, metastasis and chemoresistance in triple-negative breast cancer by regulating miR-512-3p/CDCA3 axis

“…For instance, knockdown of CDCA3 inhibited cellular proliferation by arresting cell-cycle progression at the G1 phase in oral cancer [ 30 ]. Suppression of CDCA3 decreased cell proliferative, healing, or invasive ability in gastric cancer [ 31 , 32 ]. Also, CDCA3 was reported to exert a carcinogenic effect in NSCLC and colorectal cancer via different signaling pathway [ 33 – 35 ].…”

Cell Division Cycle Associated Genes as Diagnostic and Prognostic Biomarkers in Hepatocellular Carcinoma

“…Downregulation of CDCA1 expression can inhibit the proliferation of tumor cells, while overexpression of CDCA1 is associated with poor prognosis (Hu et al, 2015). CDCA3 has been shown to promote cell proliferation and invasion through activation of the Ras signaling pathway or hypomethylation in gastric cancer cells (Zhang et al, 2019). CDCA5 plays important roles in migration, proliferation, apoptosis, and invasion of tumor cells by regulating sister chromatid segregation and cohesion (Xu et al, 2019).…”