Cell division cycle associated 5 promotes colorectal cancer progression by activating the ERK signaling pathway
Cell division cycle associated 5 promotes colorectal cancer progression by activating the ERK signaling pathway
复制标题
细胞分裂周期相关5通过激活ERK信号通路促进结直肠癌进展
DOI：
10.1038/s41389-019-0123-5
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发表时间：
2019-02-26
期刊：
影响因子：
6.2
通讯作者：
Peng, Jun
中科院分区：
文献类型：
--
作者：
Shen, Aling;Liu, Liya;Peng, Jun
细胞分裂周期相关基因5(CDCA5)与多种人类癌症的发生发展密切相关。然而，CDCA5在结直肠癌(CRC)中的功能意义尚未被研究。利用在线数据挖掘、生物化学和分子生物学相结合的方法，我们研究了CDCA5的潜在致癌活性及其潜在机制。对人体组织样本的实验表明，CDCA5在结直肠癌组织中的表达高于在非癌旁组织中的表达，并且CDCA5在结直肠癌组织中的上调与患者较短的生存期有关。此外，具有代表性的大肠癌细胞系CDCA5的表达高于胎儿结肠粘膜细胞。慢病毒介导的shRNA基因敲除CDCA5抑制了培养的HCT116和HT-29细胞的增殖和诱导其凋亡，并抑制了裸鼠移植瘤的生长。CDCA5基因敲除可降低CDK1和CyclinB1的表达，提高caspase-3活性，裂解PARP和Bax/Bcl2比值。CDCA5基因敲除也显著降低ERK1/2的磷酸化和c-jun的表达。综上所述，这些发现提示，可能通过激活ERK信号通路，在CRC的进展中起着重要作用。
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.