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Identification of a long non-coding RNA regulator of liver carcinoma cell survival
Name
s41419-021-03453-w.pdf
Description
Published version
Size
1.84 MB
Format
Adobe PDF
Checksum (MD5)
4f2799cec0d069b828838d66c832b3a8
Author(s)
Rybakova, Yulia
Gonzalez, John T
Bogorad, Roman
Chauhan, Vikash P
Dong, Yize L
Whittaker, Charles A
Zatsepin, Timofei
Koteliansky, Victor
Anderson, Daniel G
Date Issued
2021
Journal
Cell Death and Disease
Publisher
Springer Science and Business Media LLC
Version
Final published version
Abstract
© 2021, The Author(s). 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.
Terms of Use
Creative Commons Attribution 4.0 International license
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DOI of Published Version
10.1038/s41419-021-03453-w
