SPZ1 promotes deregulation of Bim to boost apoptosis resistance in colorectal cancer

Liu, Xiao-Yu1,2,3,4; Zheng, Chang-Bo5,6; Wang, Teng7; Xu, Jian1,2; Zhang, Meng8; Gou, Ling-Shan9; Jin, Linfang7; Qi, Xiaowei7; Zeng, Xianhai1,2; Li, Hongwen1,2; Qiu, Shuqi1,2; Zhang, Peng1,2

2020-01

10.1042/CS20190865

CLINICAL SCIENCE   影响因子和分区

0143-5221

1470-8736

Colorectal cancer (CRC) is the third most common malignancies in adults. Similar to other solid tumors, CRC cells show increased proliferation and suppressed apoptosis during the development and progression of the disease. Previous studies have shown that a novel tumor oncogene, spermatogenic basic helix-loop-helix transcription factor zip 1 (SPZ1), can promote proliferation. However, it is unclear whether SPZ1 plays a role in suppressing apoptosis, and the molecular mechanism behind SPZ1's suppression of apoptosis in CRC remains unclear. Here, we found that silencing endogenous SPZ1 inhibits cell growth and induces apoptosis, and overexpression of SPZ1 promotes cell growth. These findings were corroborated by in vitro and in vivo studies. Interestingly, SPZ1 overexpressing cells were resistant to 5-fluorouracil, a drug commonly used to treat cancer. Moreover, knocking down SPZ1 led to the activation of caspase through the deregulation of Bim by ERK1/2, we found that CRC tissues had significantly higher SPZ1 and lower Bim expression, and SPZ1(H)Bim(L) were associated with advanced clinical stage of CRC. Collectively, our findings demonstrate that SPZ1 contributes to tumor progression by limiting apoptosis. SPZ1 reduces apoptosis by altering the stability of Bim, suggesting SPZ1 may serve as a biomarker and therapeutic target for CRC.

SCI

英语

其他

Yunnan Provincial Education Department[2018JS163]

Research & Experimental Medicine

Medicine, Research & Experimental

WOS:000512417900005

PORTLAND PRESS LTD

CLINICAL MEDICINE

Web of Science

1.Longgang ENT Hosp, Shenzhen, Guangdong, Peoples R China
2.Inst ENT, Shenzhen Key Lab ENT, Shenzhen, Guangdong, Peoples R China
3.Jiangnan Univ, Sch Med, Wuxi, Jiangsu, Peoples R China
4.Southern Univ Sci & Technol, Sch Med, Shenzhen, Guangdong, Peoples R China
5.Kunming Med Univ, Sch Pharmaceut Sci, Kunming, Yunnan, Peoples R China
6.Kunming Med Univ, Yunnan Key Lab Pharmacol Nat Prod, Kunming, Yunnan, Peoples R China
7.Jiangnan Univ, Affiliated Hosp, Dept Oncol, Wuxi, Jiangsu, Peoples R China
8.Direct Genom Co Ltd, Shenzhen, Guangdong, Peoples R China
9.Xuzhou Matern & Child Hlth Care Hosp, Xuzhou, Jiangsu, Peoples R China

Liu, Xiao-Yu,Zheng, Chang-Bo,Wang, Teng,et al. SPZ1 promotes deregulation of Bim to boost apoptosis resistance in colorectal cancer[J]. CLINICAL SCIENCE,2020,134(2):155-167.

Liu, Xiao-Yu.,Zheng, Chang-Bo.,Wang, Teng.,Xu, Jian.,Zhang, Meng.,...&Zhang, Peng.(2020).SPZ1 promotes deregulation of Bim to boost apoptosis resistance in colorectal cancer.CLINICAL SCIENCE,134(2),155-167.

Liu, Xiao-Yu,et al."SPZ1 promotes deregulation of Bim to boost apoptosis resistance in colorectal cancer".CLINICAL SCIENCE 134.2(2020):155-167.