Abstract
Stress granules (SGs) are stalled translation initiation complexes comprising untranslated mRNAs and RNA-binding proteins (RBPs). RBP fox-1 homolog 2 (Rbfox2), a component of SGs, binds to retinoblastoma 1 (RB1) mRNA, which is closely related to cancer progression; however, the role of Rbfox2 in cancer progression remains largely unknown. In this study, we confirmed that Rbfox2, which is present in the nucleus as a splicing regulator, localizes to the cytoplasm of human colon cancer tissues and that induction of Rbfox2 dissociation from SGs by resveratrol treatment inhibits cancer progression. We also observed that Rbfox2 in SGs inhibited RB1 protein expression and promoted cell cycle progression. Additionally, resveratrol treatment inhibited SG-mediated Rbfox2 localization, further inhibiting RB1 protein expression, and inhibited specific Rbfox2 localization to the cytoplasm in melanoma B16-F10 cells, thereby effectively inhibiting metastasis and tumor growth ability. These results indicate that Rbfox2 dissociation from SGs attenuates cancer progression and offer insight into the mechanism associated with Rbfox2 dissociation, thereby marking Rbfox2 as a potential candidate target for cancer therapy.
Highlights
Introduction Nascent mRNAs bind toRNA-binding proteins (RBPs) to form a complex of ribonucleoprotein particles (RNPs)[1]
We have previously shown that RBP fox-1 homolog 2 (Rbfox2), a typical RBP that regulates alternative premRNA splicing in the nucleus, binds to the mRNA of cell cycle-related genes, including retinoblastoma 1 (RB1), in SGs22
The results suggest that the subcellular localization of Rbfox[2] to the cytoplasm is cancer cell-specific
Summary
RNA-binding proteins (RBPs) to form a complex of ribonucleoprotein particles (RNPs)[1]. In the RNP complex, RBPs play an important role in gene expression by determining mRNA decay/stabilization, subcellular localization, and translation rates[2,3,4]. RNP granules formed by the aggregation of RBPs and RNAs form non-membrane-bound cellular compartments. Depending on their composition, subcellular localization, response to stimuli, and function, RNP granules can contain processing bodies, stress granules (SGs), neuronal granules, and nuclear paraspeckles[5,6,7]. Recent studies have reported that SGs contain signaling and catalytic proteins as well as transcripts and translation components, suggesting that rearrangement of RNP complexes by SG assembly and disassembly can critically affect cell metabolism and survival[1]. T-cell intracytoplasmic antigen-1 (TIA-1)-related protein, tristetraprolin, and
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
