Abstract
Cell division cycle associated 5 (CDCA5) is implicated in the development and progression of a variety of human cancers. Functional significance of CDCA5 in colorectal cancer (CRC), however, has not been investigated. Using a combination of on-line data mining, biochemistry, and molecular biology, we examined the potential oncogenic activity of CDCA5 and the underlying mechanisms. Experiments with human tissue sample showed increased CDCA5 expression in CRC vs. in noncancerous adjacent tissue, and association of CDCA5 upregulation in CRC tissues with shorter patient survival. Also, representative CRC cell-lines had higher CDCA5 expression vs. fetal colonic mucosal cells. CDCA5 knockdown using lentivirus-mediated shRNA inhibited the proliferation and induced apoptosis in cultured HCT116 and HT-29 cells, and suppressed the growth of xenograft in nude mice. CDCA5 knockdown decreased the expression of CDK1 and CyclinB1, increased caspase-3 activity, cleaved PARP and the Bax/Bcl-2 ratio. CDCA5 knockdown also significantly decreased phosphorylation of ERK1/2 and expression of c-jun. Taken together, these findings suggest a significant role in CRC progression of CRC, likely by activating the ERK signaling pathway.
Highlights
Colorectal cancer (CRC) is the third leading cause of cancer-related death worldwide[1]
Similar results were obtained with online data mining using the R2 Bioinformatic Platform and TCGA (Fig. 1c, d). Quantitative real-time polymerase chain reaction (qPCR) and Western-blot analyses of cultured human CRC cell lines (Caco-2, HT-29, RKO, HCT116, and HCT-8) showed significantly higher Cell division cycle associated 5 (CDCA5) expression in CRC cells than in fetal colonic mucosal cells (FHC) (Fig. 1e, f; P < 0.05)
The first major finding in the current study is the overexpression of CDCA5 in CRC tissues vs. in adjacent noncancerous tissues
Summary
Colorectal cancer (CRC) is the third leading cause of cancer-related death worldwide[1]. Despite recent advances in early diagnosis of and treatments for CRC, patient mortality remains high. Uncontrolled growth is a key feature of cancers[2,3]. Suppressing the proliferation of cancer cells represent an important strategy in anticancer treatment. Proliferation is primarily regulated by cell cycle[4] that contains three major checkpoints—one at the G1–S transition and two at G2–M transition[5].
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