PVT1 is a stress-responsive lncRNA that drives ovarian cancer metastasis and chemoresistance

Kevin Tabury, Mehri Monavarian, Eduardo Listik, Abigail K. Shelton, Alex Seok Choi, Roel Quintens, Rebecca C Arend, Nadine Hempel, Ryan C Miller, Balázs Györrfy, Karthikeyan Mythreye

    Research outputpeer-review


    Metastatic growth of ovarian cancer cells into the peritoneal cavity requires adaptation to various cellular stress factors to facilitate cell survival and growth. Here, we demonstrate the role of PVT1, one such stress induced long non-coding RNA, in ovarian cancer growth and metastasis. PVT1 is an amplified and overexpressed lncRNA in ovarian cancer with strong predictive value for survival and response to targeted therapeutics. We find that expression of PVT1 is regulated by tumor cells in response to
    cellular stress, particularly loss of cell–cell contacts and changes in matrix rigidity occurring in a YAP1-dependent manner. Induction
    of PVT1 promotes tumor cell survival, growth, and
    migration. Conversely, reducing PVT1 levels robustly abrogates
    metastatic behavior and tumor cell dissemination in cell lines and
    syngeneic transplantation models in vivo. We find that reducing
    PVT1 causes widespread changes in the transcriptome leading to
    alterations in cellular stress response and metabolic pathways
    including doxorubicin metabolism, which impacts chemosensitivity.
    Together, these findings implicate PVT1 as a promising therapeutic
    target to suppress metastasis and chemoresistance in
    ovarian cancer.
    Original languageEnglish
    Article number2022013170
    Pages (from-to)1-17
    Number of pages17
    JournalLife Science Alliance
    Issue number11
    StatePublished - 12 Jul 2022

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