LncRNA HOTAIR recruits SNAIL to inhibit the transcription of HNF4? and promote the viability, migration, invasion and EMT of colorectal cancer.

ABSTRACT: Colorectal cancer causes severe burdensome on the health by its high fatality and poor prognosis. Hox transcript antisense intergenic RNA (HOTAIR) was believed closely related with the genesis and development of colorectal cancer, but the regulatory mechanism is still to be investigated. The expression of HOTAIR was analyzed in colorectal cancer using both qRT-PCR and ISH assay. The cell viability, migration, invasion and apoptosis rate were evaluated using MTT, BrdU,Transwell and flow cytometryexperiments. The interaction between HOTAIR and SNAIL was detected using RIP and RNA pull-down. The binding of SNAIL to HNF4? promoter was assessed by ChIP. The cell lines that knock down HOTAIR, SNAIL or overexpress HNF4? were constructed using retroviral vector system. The tumorigenic and metastatic capacity of colorectal cancer cells after knocking down HOTAIR were evaluated based on xenograft assay and liver metastases model. HOTAIR was highly expressed in both tissue and cell lines of colorectal cancer, indicated a regulatory function in colorectal cancer. Knock-down of HOTAIR suppressed cell viability, migration, invasion and epithelial-mesenchymal transition (EMT) of colorectal cancer cells in vitro, and inhibited the growth and metastasis of colorectal tumor in nude mice. We further found that HOTAIR suppressed HNF4? via recruiting SNAIL, and the overexpression of HNF4? inhibited cell viability, migration, invasion and EMT of colorectal cancer cells. We demonstrated that HOTAIR regulates the level of HNF4? via recruiting SNAIL, knocking down HOTAIR repressed the cell viability and metestasis of colorectal cancer cell line in vitro, and suppressed the tomorgenesis and migration/invasion of colorectal cancer in vivo.

SUBMITTER: Jin L 

PROVIDER: S-EPMC7901038 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature