Identification and characterization of novel ETV4 splice variants in prostate cancer.


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
31 03 2023
Historique:
received: 26 09 2022
accepted: 06 02 2023
medline: 4 4 2023
entrez: 31 3 2023
pubmed: 1 4 2023
Statut: epublish

Résumé

ETV4, one of ETS proteins overexpressed in prostate cancer, promotes migration, invasion, and proliferation in prostate cells. This study identifies a series of previously unknown ETV4 alternatively spliced transcripts in human prostate cell lines. Their expression has been validated using several unbiased techniques, including Nanopore sequencing. Most of these transcripts originate from an in-frame exon skipping and, thus, are expected to be translated into ETV4 protein isoforms. Functional analysis of the most abundant among these isoforms shows that they still bear an activity, namely a reduced ability to promote proliferation and a residual ability to regulate the transcription of ETV4 target genes. Alternatively spliced genes are common in cancer cells: an analysis of the TCGA dataset confirms the abundance of these novel ETV4 transcripts in prostate tumors, in contrast to peritumoral tissues. Since none of their translated isoforms have acquired a higher oncogenic potential, such abundance is likely to reflect the tumor deranged splicing machinery. However, it is also possible that their interaction with the canonical variants may contribute to the biology and the clinics of prostate cancer. Further investigations are needed to elucidate the biological role of these ETV4 transcripts and of their putative isoforms.

Identifiants

pubmed: 37002241
doi: 10.1038/s41598-023-29484-1
pii: 10.1038/s41598-023-29484-1
pmc: PMC10066307
doi:

Substances chimiques

ETV4 protein, human 0
Proto-Oncogene Proteins 0
Proto-Oncogene Proteins c-ets 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

5267

Informations de copyright

© 2023. The Author(s).

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Auteurs

Irene Cosi (I)

Core Research Laboratory, Istituto per lo Studio, la Prevenzione e la Rete Oncologica (ISPRO), Viale Pieraccini 6, 50139, Florence, Italy.
ICCOM - National Research Council, Sesto Fiorentino, Florence, Italy.

Annalisa Moccia (A)

Core Research Laboratory, Istituto per lo Studio, la Prevenzione e la Rete Oncologica (ISPRO), Viale Pieraccini 6, 50139, Florence, Italy.

Chiara Pescucci (C)

Core Research Laboratory, Istituto per lo Studio, la Prevenzione e la Rete Oncologica (ISPRO), Viale Pieraccini 6, 50139, Florence, Italy.

Uday Munagala (U)

Core Research Laboratory, Istituto per lo Studio, la Prevenzione e la Rete Oncologica (ISPRO), Viale Pieraccini 6, 50139, Florence, Italy.

Salvatore Di Giorgio (S)

Core Research Laboratory, Istituto per lo Studio, la Prevenzione e la Rete Oncologica (ISPRO), Viale Pieraccini 6, 50139, Florence, Italy.

Irene Sineo (I)

Core Research Laboratory, Istituto per lo Studio, la Prevenzione e la Rete Oncologica (ISPRO), Viale Pieraccini 6, 50139, Florence, Italy.

Silvestro G Conticello (SG)

Core Research Laboratory, Istituto per lo Studio, la Prevenzione e la Rete Oncologica (ISPRO), Viale Pieraccini 6, 50139, Florence, Italy.
IFC - National Research Council, Pisa, Italy.

Rosario Notaro (R)

Core Research Laboratory, Istituto per lo Studio, la Prevenzione e la Rete Oncologica (ISPRO), Viale Pieraccini 6, 50139, Florence, Italy.
IFC - National Research Council, Pisa, Italy.

Maria De Angioletti (M)

Core Research Laboratory, Istituto per lo Studio, la Prevenzione e la Rete Oncologica (ISPRO), Viale Pieraccini 6, 50139, Florence, Italy. m.deangioletti@ispro.toscana.it.
ICCOM - National Research Council, Sesto Fiorentino, Florence, Italy. m.deangioletti@ispro.toscana.it.

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