Long noncoding RNA promotes oncogenic pathway to drive stem cell behaviors of hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is a notoriously malignant cancer in the liver that causes high mortality and morbidity. The poor prognosis of HCC patients is largely attributed to recently recognized stem cell behaviors of HCC. Notably, a recent study revealed a novel mechanism by which long noncoding RNA promotes oncogenic pathway to drive stem cell behaviors of HCC. Kinesin Family Member 9-Antisense RNA 1 (KIF9-AS1) is a long noncoding RNA significantly upregulated in HCC patients and its level is correlated with poor prognosis. Furthermore, m6A writer METTL3 is upregulated in HCC patients and promotes the m6A methylation and stability of KIF9-AS1. The stabilized KIF9-AS1 then promotes ubiquitin-specific peptidase 1 mediated deubiquitination of short stature homeobox (SHOX2). The stabilized SHOX2 then drives the transcription of key genes involved in Wnt/β-catenin pathway, TGFβ signaling pathway and other unclear pathways to promote stem cell behaviors of HCC. These findings bring new hope to reduce HCC mortality and morbidity by revealing METTL3/KIF9-AS1/SHOX2 axis as prognostic markers and therapeutic targets.