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

© 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 transcrip...

Full description

Bibliographic Details
Main Authors: Rybakova, Yulia, Gonzalez, John T, Bogorad, Roman, Chauhan, Vikash P, Dong, Yize L, Whittaker, Charles A, Zatsepin, Timofei, Koteliansky, Victor, Anderson, Daniel G
Format: Article
Language:English
Published: Springer Science and Business Media LLC 2021
Online Access:https://hdl.handle.net/1721.1/133329
_version_ 1811070931487948800
author Rybakova, Yulia
Gonzalez, John T
Bogorad, Roman
Chauhan, Vikash P
Dong, Yize L
Whittaker, Charles A
Zatsepin, Timofei
Koteliansky, Victor
Anderson, Daniel G
author_facet Rybakova, Yulia
Gonzalez, John T
Bogorad, Roman
Chauhan, Vikash P
Dong, Yize L
Whittaker, Charles A
Zatsepin, Timofei
Koteliansky, Victor
Anderson, Daniel G
author_sort Rybakova, Yulia
collection MIT
description © 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.
first_indexed 2024-09-23T08:43:56Z
format Article
id mit-1721.1/133329
institution Massachusetts Institute of Technology
language English
last_indexed 2024-09-23T08:43:56Z
publishDate 2021
publisher Springer Science and Business Media LLC
record_format dspace
spelling mit-1721.1/1333292021-10-28T04:54:39Z Identification of a long non-coding RNA regulator of liver carcinoma cell survival Rybakova, Yulia Gonzalez, John T Bogorad, Roman Chauhan, Vikash P Dong, Yize L Whittaker, Charles A Zatsepin, Timofei Koteliansky, Victor Anderson, Daniel G © 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. 2021-10-27T19:52:09Z 2021-10-27T19:52:09Z 2021 2021-06-04T17:47:30Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/133329 en 10.1038/s41419-021-03453-w Cell Death and Disease Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf Springer Science and Business Media LLC Nature
spellingShingle Rybakova, Yulia
Gonzalez, John T
Bogorad, Roman
Chauhan, Vikash P
Dong, Yize L
Whittaker, Charles A
Zatsepin, Timofei
Koteliansky, Victor
Anderson, Daniel G
Identification of a long non-coding RNA regulator of liver carcinoma cell survival
title Identification of a long non-coding RNA regulator of liver carcinoma cell survival
title_full Identification of a long non-coding RNA regulator of liver carcinoma cell survival
title_fullStr Identification of a long non-coding RNA regulator of liver carcinoma cell survival
title_full_unstemmed Identification of a long non-coding RNA regulator of liver carcinoma cell survival
title_short Identification of a long non-coding RNA regulator of liver carcinoma cell survival
title_sort identification of a long non coding rna regulator of liver carcinoma cell survival
url https://hdl.handle.net/1721.1/133329
work_keys_str_mv AT rybakovayulia identificationofalongnoncodingrnaregulatoroflivercarcinomacellsurvival
AT gonzalezjohnt identificationofalongnoncodingrnaregulatoroflivercarcinomacellsurvival
AT bogoradroman identificationofalongnoncodingrnaregulatoroflivercarcinomacellsurvival
AT chauhanvikashp identificationofalongnoncodingrnaregulatoroflivercarcinomacellsurvival
AT dongyizel identificationofalongnoncodingrnaregulatoroflivercarcinomacellsurvival
AT whittakercharlesa identificationofalongnoncodingrnaregulatoroflivercarcinomacellsurvival
AT zatsepintimofei identificationofalongnoncodingrnaregulatoroflivercarcinomacellsurvival
AT kotelianskyvictor identificationofalongnoncodingrnaregulatoroflivercarcinomacellsurvival
AT andersondanielg identificationofalongnoncodingrnaregulatoroflivercarcinomacellsurvival