Down-Regulation of LINC00460 Represses Metastasis of Colorectal Cancer via WWC2

Abstract

Background: Colorectal cancer (CRC) is one of the most prevalent cancers and a common cause of cancer-related death. Long noncoding RNAs have been reported to play an essential role in the development of CRC.

Aims: This study aimed to investigate the possible function of LINC00460 in CRC.

Methods: Initially, microarray-based gene expression profiling of CRC was employed to identify differentially expressed genes. Next, the expression of LINC00460 was examined and the cell line presenting with the highest LINC00460 expression was selected for subsequent experimentation. Then, the interaction among LINC00460, ERG, and WWC2 was identified. The effect of LINC00460 on proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT)-related factors as well as tumorigenicity of transfected cells was examined with gain- and loss-of-function experiments.

Results: LINC00460 was robustly induced while WWC2 was poorly expressed in CRC. In addition, LINC00460 could down-regulate WWC2 through interaction with ERG, which led to promoted invasion, migration, and EMT of CRC cells in addition to tumor growth in vivo. Besides, down-regulation of LINC00460 exerted inhibitory effect on these biological activities.

Conclusion: Taken together, the key findings of the current study provided evidence suggesting that silencing of LINC00460 could potentially suppress EMT of CRC cells by increasing WWC2 via ERG, and highlighting that knockdown of LINC00460 could serve as a therapeutic target for CRC treatment.

Keywords: Colorectal cancer; Epithelial–mesenchymal transition; LINC00460; Migration; WWC2.