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.
Sci Rep. 2023 Mar 31;13(1):5267. doi: 10.1038/s41598-023-29484-1.
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.
ETV4 是前列腺癌中过表达的 ETS 蛋白之一，它促进前列腺细胞的迁移、侵袭和增殖。本研究在人前列腺细胞系中鉴定了一系列以前未知的 ETV4 选择性剪接转录本。使用几种无偏技术，包括纳米孔测序，验证了它们的表达。这些转录本大多数源自框架外显子跳跃，因此预计会被翻译成 ETV4 蛋白异构体。对这些异构体中最丰富的异构体进行功能分析表明，它们仍然具有活性，即降低促进增殖的能力和剩余调节 ETV4 靶基因转录的能力。选择性剪接基因在癌细胞中很常见：对 TCGA 数据集的分析证实了这些新型 ETV4 转录本在前列腺肿瘤中的丰度，与肿瘤周围组织形成对比。由于它们的翻译异构体都没有获得更高的致癌潜能，因此这种丰度可能反映了肿瘤失调的剪接机制。然而，它们与典型变体的相互作用也可能有助于前列腺癌的生物学和临床。需要进一步研究来阐明这些 ETV4 转录本及其潜在异构体的生物学作用。
