The long non-coding RNA TAZ-AS202 promotes lung cancer progression via regulation of the E2F1 transcription factor and activation of Ephrin signaling.
Journal
Cell death & disease
ISSN: 2041-4889
Titre abrégé: Cell Death Dis
Pays: England
ID NLM: 101524092
Informations de publication
Date de publication:
18 11 2023
18 11 2023
Historique:
received:
10
08
2023
accepted:
06
11
2023
revised:
27
10
2023
medline:
20
11
2023
pubmed:
19
11
2023
entrez:
18
11
2023
Statut:
epublish
Résumé
Long non-coding RNAs (lncRNAs) are transcripts without coding potential that are pervasively expressed from the genome and have been increasingly reported to play crucial roles in all aspects of cell biology. They have been also heavily implicated in cancer development and progression, with both oncogenic and tumor suppressor functions. In this work, we identified and characterized a novel lncRNA, TAZ-AS202, expressed from the TAZ genomic locus and exerting pro-oncogenic functions in non-small cell lung cancer. TAZ-AS202 expression is under the control of YAP/TAZ-containing transcriptional complexes. We demonstrated that TAZ-AS202 is overexpressed in lung cancer tissue, compared with surrounding lung epithelium. In lung cancer cell lines TAZ-AS202 promotes cell migration and cell invasion. TAZ-AS202 regulates the expression of a set of genes belonging to cancer-associated pathways, including WNT and EPH-Ephrin signaling. The molecular mechanism underlying TAZ-AS202 function does not involve change of TAZ expression or activity, but increases the protein level of the transcription factor E2F1, which in turn regulates the expression of a large set of target genes, including the EPHB2 receptor. Notably, the silencing of both E2F1 and EPHB2 recapitulates TAZ-AS202 silencing cellular phenotype, indicating that they are essential mediators of its activity. Overall, this work unveiled a new regulatory mechanism that, by increasing E2F1 protein, modifies the non-small cell lung cancer cells transcriptional program, leading to enhanced aggressiveness features. The TAZ-AS202/E2F1/EPHB2 axis may be the target for new therapeutic strategies.
Identifiants
pubmed: 37980331
doi: 10.1038/s41419-023-06277-y
pii: 10.1038/s41419-023-06277-y
pmc: PMC10657417
doi:
Substances chimiques
RNA, Long Noncoding
0
E2F1 Transcription Factor
0
Ephrins
0
E2F1 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
752Informations de copyright
© 2023. The Author(s).
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