A novel long noncoding RNA lncWDR26 suppresses the growth and metastasis of hepatocellular carcinoma cells through interaction with SIX3

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. Long noncoding RNAs (lncRNAs) are involved in the tumorigenesis and progression of some cancers. However, only a handful of lncRNAs have been functionally identified in HCC. In the present study, we identified a novel functional lncRNA in HCC, termed lncWDR26 (GenBank Accession no. RP11-365O16). Here, we reported that lncWDR26 was significantly downregulated in HCC tissues and cells. Moreover, decreased lncWDR26 expression correlates with larger tumor size, higher clinical stage, and tumor metastasis, and also predicts poor prognosis in patients with HCC. In HCC cells, overexpression of lncWDR26 inhibited growth and metastasis, both in vitro and in vivo. Mechanistically, lncWDR26 suppressed HCC growth and metastasis by inhibiting WDR26 transcription. Notably, lncWDR26 was associated with SIX homeobox 3 (SIX3), and this association was required for the repression of WDR26 transcription. Together, these results indicate that lncWDR26 is a tumor suppressor lncRNA that promotes tumor progression, leading us to propose that lncRNAs may serve as key regulatory hubs in HCC progression.