Identification of a long non-coding RNA regulator of liver carcinoma cell survival

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.

GBAP1 functions as a tumor promotor in hepatocellular carcinoma via the PI3K/AKT pathway

“…For example, the lncRNA ZEB1AS1 reduces HCC proliferation by targeting miR-365a-3p [ 17 ]. The knockdown of the lncRNA ASTILCS downregulates protein tyrosine kinase 2 (PTK2), leading to HCC cell death [ 18 ].…”

Synthesis, characterization, and antiproliferative evaluation of novel sorafenib analogs for the treatment of hepatocellular carcinoma

“…[ 5 ] This dismal outlook highlights the need for innovative treatments. [ 6 ] The majority of instances of liver cancer are presented as HCC, although secondary liver cancers develop from metastases that originate from tumors located in other parts of the body, most frequently in the gastrointestinal system. [ 7 8 ]…”

The Role of Long Non-Coding RNA and microRNA Networks in Hepatocellular Carcinoma and Its Tumor Microenvironment

“…Recently, an increasing number of studies have focused on the emerging roles of lncRNAs and miRNAs in HCC and the tumor microenvironment [ 16 , 17 , 18 ]. In this review, the lncRNA and miRNA networks in HCC and the tumor microenvironment have been discussed.…”