LncRNA CRNDE promotes hepatocellular carcinoma progression by upregulating SIX1 through modulating miR-337-3p.

BACKGROUND

Long noncoding RNA (lncRNA) is emerging as a vital regulator in various cancers. Recently, it was found that lncRNA colorectal neoplasia differentially expressed (CRNDE) plays an oncogenic role, promoting cell proliferation and migration in hepatocellular carcinoma (HCC). However, the underlying regulatory mechanism of lncRNA CRNDE remains unclear.

METHODS

The expression levels of lncRNA CRNDE and miR-337-3p were analyzed by real-time polymerase chain reaction, and sineoculis homeobox homolog 1 (SIX1) expression was determined by Western blot analysis. RNA pull-down, luciferase and Western blot analysis assays were used to examine the target relationship between lncRNA CRNDE and miR-337-3p as well as between miR-337-3p and SIX1. The functional effects of lncRNA CRNDE and miR-337-3p were examined in vitro by using cell viability, colony formation, wound scratch, transwell assays, and in vivo in a xenograft tumor mouse model.

RESULTS

LncRNA CRNDE was overexpressed in tumor tissues of patients with HCC. LncRNA CRNDE downregulation significantly suppressed cell proliferation and migration. Mechanistic investigations demonstrated that lncRNA CRNDE interacted with miR-337-3p and decreased its expression, thereby increasing the protein expression of miR-337-3p's target, SIX1. In addition, in vivo experiments using a xenograft tumor mouse model revealed that lncRNA CRNDE served as an oncogene, partly through sponging miR-337-3p and upregulating SIX1 in HCC.

CONCLUSIONS

In this study, we report a newly identified regulatory mechanism lncRNA CRNDE/miR-337-3p/SIX1 axis, suggesting a promising therapeutic target in HCC.