Abstract
Genomic studies have significantly improved our understanding of hepatocellular carcinoma (HCC) biology and have led to the discovery of multiple protein-coding genes driving hepatocarcinogenesis. In addition, these studies have identified thousands of new non-coding transcripts deregulated in HCC. We hypothesize that some of these transcripts may be involved in disease progression. Long non-coding RNAs are a large class of non-coding transcripts which participate in the regulation of virtually all cellular functions. However, a majority of lncRNAs remain dramatically understudied. Here, we applied a pooled shRNA-based screen to identify lncRNAs essential for HCC cell survival. We validated our screening results using RNAi, CRISPRi, and antisense oligonucleotides. We found a lncRNA, termed ASTILCS, that is critical for HCC cell growth and is overexpressed in tumors from HCC patients. We demonstrated that HCC cell death upon ASTILCS knockdown is associated with apoptosis induction and downregulation of a neighboring gene, protein tyrosine kinase 2 (PTK2), a crucial protein for HCC cell survival. Taken together, our study describes a new, non-coding RNA regulator of HCC.
Highlights
Liver cancer is one of the leading causes of cancer mortality worldwide, accounting for more than 700,000 deaths per year[1]
Applying stringent filtering criteria and three-step validation we identified Long non-coding RNAs (lncRNAs) ASTILCS (ENST00000501440.1) to be important for survival of Hepatocellular carcinoma (HCC) cells
To the best of our knowledge, we provide the first characterization of the lncRNA ASTILCS
Summary
Liver cancer is one of the leading causes of cancer mortality worldwide, accounting for more than 700,000 deaths per year[1]. Hepatocellular carcinoma (HCC) is the most frequent subtype of liver cancer. Despite recent progress in HCC treatment it remains one of the deadliest types of cancer[1,2]. The incidence of HCC has been increasing in recent decades, making HCC one of the fastest-growing causes of death worldwide[3]. This poor prognosis underlines the need for new effective therapies. Better understanding of the molecular mechanisms regulating HCC progression may yield new potential drug targets
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