AR and ERG drive the expression of prostate cancer specific long noncoding RNAs

Annika Kohvakka, Mina Sattari, Anastasia Shcherban, Matti Annala, Alfonso Urbanucci, Juha Kesseli, Teuvo L. J. Tammela, Kati Kivinummi, Leena Latonen, Matti Nykter, Tapio Visakorpi

    Research output: Contribution to journalArticleScientificpeer-review

    1 Citation (Scopus)

    Abstract

    Long noncoding RNAs (lncRNAs) play pivotal roles in cancer development and progression, and some function in a highly cancer-specific manner. However, whether the cause of their expression is an outcome of a specific regulatory mechanism or nonspecific transcription induced by genome reorganization in cancer remains largely unknown. Here, we investigated a group of lncRNAs that we previously identified to be aberrantly expressed in prostate cancer (PC), called TPCATs. Our high-throughput real-time PCR experiments were integrated with publicly available RNA-seq and ChIP-seq data and revealed that the expression of a subset of TPCATs is driven by PC-specific transcription factors (TFs), especially androgen receptor (AR) and ETS-related gene (ERG). Our in vitro validations confirmed that AR and ERG regulated a subset of TPCATs, most notably for EPCART. Knockout of EPCART was found to reduce migration and proliferation of the PC cells in vitro. The high expression of EPCART and two other TPCATs (TPCAT-3-174133 and TPCAT-18-31849) were also associated with the biochemical recurrence of PC in prostatectomy patients and were independent prognostic markers. Our findings suggest that the expression of numerous PC-associated lncRNAs is driven by PC-specific mechanisms and not by random cellular events that occur during cancer development. Furthermore, we report three prospective prognostic markers for the early detection of advanced PC and show EPCART to be a functionally relevant lncRNA in PC.

    Original languageEnglish
    Pages (from-to)5241–5251
    Number of pages11
    JournalOncogene
    Volume39
    DOIs
    Publication statusPublished - 2020
    Publication typeA1 Journal article-refereed

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    • Publication forum level 2

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