Hepatocellular carcinoma (HCC) is the predominant subject of liver malignancies which provoke global concern. Previous studies have shown that long non-coding RNAs (lncRNAs) are differentially expressed in HCC, which have distinct functional roles in the pathogenesis of HCC. Recent advance of high-throughput RNA sequencing have revealed that numerous non-coding RNAs are expressed in cancers. Here, to deleineate functional lncRNAs in HCC, RNA-seq profiling was performed. I found 23 differentially expressed lncRNAs in the HCCs compared to non-tumoral tissues. Of these, 15 lncRNAs showed the correlated expression between antisense and sense lncRNAs, inclduding HAND2-AS1 and HAND2. The functional effects of HAND2-AS1 or HAND2 expression in liver cancers were further evaluated. Overexpression of HAND2-AS1 or HAND2 inhibited the proliferation and migration of liver cancer cells in vitro. The xenografted in vivo mouse model also showed significant reduction of tumor size by knockdown of HAND2. In addition, I found that the HAND2 mRNA expression was induced by HAND2-AS1 overexpression. This HAND2-AS1-mediated HAND2 expression was mediated throguht phosphorylation of CREB transcription factor.
In summary, genome-wide noncoding RNA profiling analysis could identify that HAND2-AS1 can play pivotal roles in liver cancer progression.