4.7 Article

The RNA-Binding Protein CELF2 Inhibits Ovarian Cancer Progression by Stabilizing FAM198B

Journal

MOLECULAR THERAPY-NUCLEIC ACIDS
Volume 23, Issue -, Pages 169-184

Publisher

CELL PRESS
DOI: 10.1016/j.omtn.2020.10.011

Keywords

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Funding

  1. National Natural Science Foundation of China [81972431, 81902641, 81902640]
  2. Science and Technology Commission of Shanghai Municipality [KW1711]
  3. Shanghai Sailing Program [20YF1408000]
  4. Shanghai Anticancer Association EYAS PROJECT [SACACY19A07]

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This study identified downregulation of CELF2 in ovarian cancer, which correlated with patient survival and affected cell proliferation and metastasis through regulation of FAM198B and the MAPK/ERK signaling pathway. Additionally, curcumin-induced increase in CELF2 expression enhanced ovarian cancer cell sensitivity to cisplatin, providing potential therapeutic targets for ovarian cancer.
An increasing number of studies have clarified the functional roles of RNA-binding proteins (RBPs) in driving post -transcriptional mechanisms of cancer progression. In this study, we integrated data from the RBP database and Gene Expression Omnibus (GEO) data with RNA sequencing (RNA-seq) data from 10 ovarian cancer tissues and 8 normal ovarian tissues and identified an RBP, CUGBP-and ETR-3-like family 2 (CELF2). We found that CELF2 expression was downregulated in ovarian cancer and positively correlated with the overall survival (OS) and progression-free survival (PFS) of patients with ovarian cancer. Altered CELF2 expression led to changes in the proliferation, migration, and invasion of ovarian cancer cells in vitro and in vivo. CELF2 expression increased the stability of its target, FAM198B, by binding to AU/U-rich elements (AREs) in the 3' untranslated region (3' UTR). FAM198B knockdown restored the CELF2-mediated suppression of proliferation and migration. We also found that CELF2/FAM198B may repress ovarian cancer progression by inhibiting the mitogen-activated protein kinase/extracellular-regulated protein kinase (MAPK/ERK) signaling pathway. Finally, a curcumin-induced increase in CELF2 expression resulted in increased ovarian cancer cell sensitivity to cisplatin. Our study elucidated a novel mechanism by which the CELF2/FAM198B axis regulates proliferation and metastasis in ovarian cancer, providing novel, potential therapeutic targets for ovarian cancer.

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