Downregulation of CDCA3 expression inhibits tumor formation in pancreatic cancer

Abstract

Downregulation of cell division cycle-associated 3 (CDCA3) markedly inhibited cell growth and induced apoptosis in tumors. However, the effect of CDCA3 in pancreatic cancer (PAC) was rarely investigated. Therefore, this study attempted to clarify the role of CDCA3 in PAC. The mRNA and protein expression of CDCA3 were examined in PAC cell lines and tumor tissues by using real-time quantitative PCR (RT-qPCR), western blotting (WB), and immunohistochemistry (IHC). The effects of CDCA3 downregulation on cell proliferation, apoptosis, and colony information were investigated through MTT assay, Annexin V-APC single staining cell apoptosis detection, and colony formation test. The microarray and ingenuity pathway ana lysis were employed to explore the potential regulato ry relation. The tumor xenograft model was established for determining the effect of CDCA3 downregulation on the growth of PAC in vivo. The results showed that the expression of CDCA3 in tumor tissues wa s higher than that of normal tissues (P < 0.05). In addition, the mRNA expression of CDCA3 was markedly increased in PANC-1 cells and SW 1990 cells when compared with human pancreatic duct epithelial (HPDE) cells (P < 0.05). MTT assay showed that the cell proliferation of PANC-1 cells and SW1990 cells was significantly inhibited after the lentivirus transfection of CDCA3 knockdown (P < 0.05). Annexin V-APC apoptosis assays suggested that the apoptotic cell number was markedly increased in the shCDCA3 group compared to that in the shCtrl group in SW1990 cells and PANC-1 cells (P < 0.05). Meanwhile, the activity of caspase-3/7 was obviously elevated in the shCDCA3 group compared to the shCtrl group (P < 0.05). The colony formation was notably inhibited in the shCDCA3 group relatively to the shCtrl group in SW1990 cells (P < 0.05). Moreover, the tumor growth was evidently suppressed in shCDCA3 group compared with shCtrl group in vivo (P < 0.05). These findings revealed that CDCA3 plays a crucial role in the progress of PCA by regulating cell apoptosis and proliferation, which may serve as a potential target for PAC treatment.

Integrate analysis of the promote function of Cell division cycle-associated protein family to pancreatic adenocarcinoma

“…Hu et al 38 found that the increased NUF2 expression in PAAD and determined that NUF2 could alter the proliferation and apoptosis of PAAD cell lines through LncRNA-AF339813. Zou et al 39 revealed that CDCA3 expression was increased in the PAAD cell lines compared to normal human pancreatic duct epithelial cells, suggesting that knocking down CDCA3 can inhibit cell proliferation and promote cell apoptosis. Wang et al 40 revealed increased CDCA2 expression in PAAD tumors, and univariate analysis showed that increased CDCA2 expression is a risk factor for PAAD patients.…”

Suppression of CDCA3 inhibits prostate cancer progression via NF‑κB/cyclin D1 signaling inactivation and p21 accumulation

“…Previous have determined that CDCA3 expression levels are increased in tumor tissues and associated with a poor patient prognosis in CRC, GC, NSCLC, OSCC and PAC (13)(14)(15)(16)(17)(18). In CRC, CDCA3 regulates E2F transcription factor 1, thereby inhibiting the expression of p21.…”

“…CDCA3 regulates cell cycle processes and serves a role in triggering mitosis entry. CDCA3 is frequently upregulated in tumor tissues and is associated with the oncogenic properties of a variety of cancers, including colorectal cancer (CRC) (13,14), gastric cancer (GC) (15), non-small cell lung cancer (NSCLC) (16), oral squamous cell carcinoma (OSCC) (17) and pancreatic cancer (PAC) (18). It has also been reported that CDCA3 acts as a downstream target gene of HOXB3, which promotes prostate cancer progression (19).…”

CDCA3 Is a Novel Prognostic Biomarker Associated with Immune Infiltration in Hepatocellular Carcinoma

“…CDCA3 can regulate E2F1 expression to influence growth and progression [31]. Many studies have elucidated the role of CDCA3 expression in diverse tumors; for instance, CDCA3 inhibits the formation of tumors by affecting cell growth and inducing apoptosis in pancreatic cancer [32]. CDCA3 expression affects other cancers as well, such as renal cell carcinoma [33], breast cancer [34], acute myeloid leukemia [35], and non-small-cell lung cancer [5].…”