The RNA-binding protein FXR1 modulates prostate cancer progression by regulating FBXO4

Cao, Hongwen; Gao, Renjie; Yu, Chao; Chen, Lei; Feng, Yigeng

doi:10.1007/s10142-019-00661-8

Cited by 33 publications

(26 citation statements)

References 20 publications

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“…More recent studies have linked FXR proteins to cancer progression, and in particular, FMRP and FXR1 were found overexpressed in different types of cancer (Lucá et al, 2013;Jin et al, 2016;Zalfa et al, 2017;Cao et al, 2019). Although many overlapping functions have been proposed for this protein family, different tissue, cellular and intracellular distributions of the FXR proteins suggest that they might have, in addition to their canonical role as RNA-binding proteins, independent functions (Darnell et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Spatial control of nucleoporin condensation by fragile X‐related proteins

et al. 2020

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Nucleoporins (Nups) build highly organized nuclear pore complexes (NPCs) at the nuclear envelope (NE). Several Nups assemble into a sieve-like hydrogel within the central channel of the NPCs. In the cytoplasm, the soluble Nups exist, but how their assembly is restricted to the NE is currently unknown. Here, we show that fragile X-related protein 1 (FXR1) can interact with several Nups and facilitate their localization to the NE during interphase through a microtubule-dependent mechanism. Downregulation of FXR1 or closely related orthologs FXR2 and fragile X mental retardation protein (FMRP) leads to the accumulation of cytoplasmic Nup condensates. Likewise, models of fragile X syndrome (FXS), characterized by a loss of FMRP, accumulate Nup granules. The Nup granule-containing cells show defects in protein export, nuclear morphology and cell cycle progression. Our results reveal an unexpected role for the FXR protein family in the spatial regulation of nucleoporin condensation.

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Section: Introductionmentioning

confidence: 99%

Spatial control of nucleoporin condensation by fragile X‐related proteins

et al. 2020

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“…Among posttranscriptional regulators, RNA‐binding proteins (RBP) are the master regulators of mRNA processing and translation, regulating RNA splicing, polyadenylation, stability, translation and degradation . To date, a variety of RBP have been reported to be involved in the regulation of prostate cancer pathogenesis or progression, which has become a new hotspot for research . Furthermore, studies have begun to focus on RBPs that participate in AR mRNA stability or splicing.…”

Section: Introductionmentioning

confidence: 99%

RNA‐binding protein Musashi2 stabilizing androgen receptor drives prostate cancer progression

et al. 2020

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This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. AbstractThe androgen receptor (AR) pathway is critical for prostate cancer carcinogenesis and development; however, after 18-24 months of AR blocking therapy, patients invariably progress to castration-resistant prostate cancer (CRPC), which remains an urgent problem to be solved. Therefore, finding key molecules that interact with AR as novel strategies to treat prostate cancer and even CRPC is desperately needed. In the current study, we focused on the regulation of RNA-binding proteins (RBPs) associated with AR and determined that the mRNA and protein levels of AR were highly correlated with Musashi2 (MSI2) levels. MSI2 was upregulated in prostate cancer specimens and significantly correlated with advanced tumor grades. Downregulation of MSI2 in both androgen sensitive and insensitive prostate cancer cells inhibited tumor formation in vivo and decreased cell growth in vitro, which could be reversed by AR overexpression. Mechanistically, MSI2 directly bound to the 3′-untranslated region (UTR) of AR mRNA to increase its stability and, thus, enhanced its transcriptional activity. Our findings illustrate a previously unknown regulatory mechanism in prostate cancer cell proliferation regulated by the MSI2-AR axis and provide novel evidence towards a strategy against prostate cancer. K E Y W O R D Sandrogen receptor, mRNA stability, Musashi2, novel anti-androgen therapy, prostate cancer

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“…FXRs can affect RNA stability, transport, or translational efficiency [111], by binding to RNA structures such as AU-rich elements (AREs) [112] and G4s [113]. FXR1 is overexpressed in different tumors [114][115][116][117], playing an essential role in cell cycle progressions and senescence bypassing. Majumder and colleagues showed that in oral cancer cells FXR1 binds and stabilized TERC thus influencing telomerase activity [110].…”

Section: Terc-interacting Proteins: the Usual And Unusual Suspectsmentioning

confidence: 99%

How RNAi machinery enters the world of telomerase

2019

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Human telomerase holoenzyme consists of the catalytic component TERT and the template RNA TERC. However, a network of accessory proteins plays key roles in its assembly, localization and stability. Defects in genes involved in telomerase biology affect the renewal of critical stem cell populations and cause disorders such as telomeropathies. Moreover, activation of telomerase in somatic cells allows neoplastic cells to proliferate indefinitely, thus contributing to tumorigenesis. For these reasons, identification of new players involved in telomerase regulation is crucial for the determination of novel therapeutic targets and biomarkers. In the very last years, increasing evidence describes components of the RNAi machinery as a new layer of complexity in human telomerase activity. In this review, we will discuss how AGO2 and other proteins which collaborate with AGO2 in RNAi pathway play a pivotal role in TERC stability and function. ARTICLE HISTORY

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The RNA-binding protein FXR1 modulates prostate cancer progression by regulating FBXO4

Cited by 33 publications

References 20 publications

Spatial control of nucleoporin condensation by fragile X‐related proteins

Spatial control of nucleoporin condensation by fragile X‐related proteins

RNA‐binding protein Musashi2 stabilizing androgen receptor drives prostate cancer progression

How RNAi machinery enters the world of telomerase

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