Knockdown of ZEB2-AS1 inhibits cell invasion and induces apoptosis in colorectal cancer.

Xiongjian Wu, Haiyan Zhu, Yuan Xie, Xiaoxiang Gu, Lei Zhang, Lixing Huang

Journal of B.U.ON. : official journal of the Balkan Union of Oncology 2020 Jan-Feb

filter terms:

To uncover the potential function of long non-coding RNA (lncRNA) ZEB2-AS1 in the progression of colorectal cancer (CRC), and its underlying mechanism. Relative level of ZEB2-AS1 in CRC tissues and matched normal ones was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Correlation between ZEB2-AS1 level and survival of CRC patients was analyzed by Kaplan-Meier method. Regulatory effects of ZEB2-AS1 on cellular behaviors of CRC cells were evaluated. The interactions between ZEB2-AS1 with LSD1 and EZH2 were explored by RNA immunoprecipitation (RIP) assay. 5-Ethynyl-2'- deoxyuridine (EdU) assay was performed to elucidate the roles of ZEB2-AS1, LSD1 and EZH2 on the proliferative ability of CRC cells. Finally, Spearman's correlation analysis was performed to analyze the relationship between ZEB2-AS1 level and expressions of proliferation- and invasion-related genes. ZEB2-AS1 was upregulated in CRC tissues relative to matched controls. Its level remained higher in CRC patients with ≥6 cm in tumor size, nodal metastasis and stage III-IV. CRC patients with low-level ZEB2-AS1 presented worse survival compared with those with high-level ZEB2-AS1. QRT-PCR data showed higher abundance of ZEB2-AS1 in CRC cell lines than colonic epithelial cell line. Knockdown of ZEB2-AS1 attenuated the proliferative, migratory and invasive abilities, but induced apoptosis of DLD1 and SW620 cells. RIP assay demonstrated the interaction between ZEB2-AS1 and LSD1, EZH2. Moreover, EdU assay revealed that transfection of sh-ZEB2-AS1 attenuated the proliferative ability, which was further reduced after co-transfection of sh-LSD1 or sh-EZH2. Finally, correlation analysis showed that mRNA level of ZEB2-AS1 was positively correlated to those of LSD1, EZH2, MMP9, MMP12 and KRAS, but negatively correlated to KLF2. LncRNA ZEB2-AS1 is upregulated in CRC. It accelerates CRC cells to proliferate via interacting with EZH2 and LSD1, thus promoting the progression of CRC.

Citation

Xiongjian Wu, Haiyan Zhu, Yuan Xie, Xiaoxiang Gu, Lei Zhang, Lixing Huang. Knockdown of ZEB2-AS1 inhibits cell invasion and induces apoptosis in colorectal cancer. Journal of B.U.ON. : official journal of the Balkan Union of Oncology. 2020 Jan-Feb;25(1):194-201