Fu Guanghou, Xu Zhijie, Chen Xiaoyi, Pan Hao, Wang Yiming, Jin Baiye
Department of Urology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, China.
J Cancer. 2020 Feb 10;11(9):2408-2420. doi: 10.7150/jca.35372. eCollection 2020.
Bladder cancer (BC) is one of the most prevalent cancers worldwide and has high rates of relapse and progression. Cell division cycle associated 5 (CDCA5), a substrate of the anaphase-promoting complex, was reported to be upregulated in several types of cancer; however, the function of CDCA5 in BC remains unclear. In this study, we observed that BC tissues had higher levels of CDCA5 expression than adjacent normal tissues. We also found that high CDCA5 expression in patients was associated with poor survival rates. An in vitro study showed that knockdown of CDCA5 in T24 and 5637 cells reduced cell proliferation and induced apoptosis in T24 and 5637 cells, while overexpression of CDCA5 in UMUC3 cells caused the opposite effects. In an additional experiment, we found that CDCA5 promoted cell proliferation by upregulating two key cell cycle factors, cell division cycle protein 2 (CDC2) and cyclin B1, and by activating the PI3K/AKT/mTOR pathway. Furthermore, CDCA5 regulate cancer cell apoptosis through the mitochondrial apoptosis pathway. In conclusion, CDCA5 plays a pivotal role in the proliferation of BC cells. A better understanding of CDCA5 may provide new insights into its role as a therapeutic target for BC.
膀胱癌（BC）是全球最常见的癌症之一，复发率和进展率都很高。细胞分裂周期相关蛋白5（CDCA5）是后期促进复合物的一个底物，据报道在几种类型的癌症中表达上调；然而，CDCA5在膀胱癌中的功能仍不清楚。在本研究中，我们观察到膀胱癌组织中CDCA5的表达水平高于相邻正常组织。我们还发现，患者中CDCA5的高表达与较差的生存率相关。一项体外研究表明，敲低T24和5637细胞中的CDCA5可降低细胞增殖并诱导T24和5637细胞凋亡，而在UMUC3细胞中过表达CDCA5则产生相反的效果。在另一项实验中，我们发现CDCA5通过上调两个关键的细胞周期因子，即细胞分裂周期蛋白2（CDC2）和细胞周期蛋白B1，并激活PI3K/AKT/mTOR通路来促进细胞增殖。此外，CDCA5通过线粒体凋亡途径调节癌细胞凋亡。总之，CDCA5在膀胱癌细胞的增殖中起关键作用。对CDCA5的更好理解可能为其作为膀胱癌治疗靶点的作用提供新的见解。
