Roles of nucleolin

Chen, Zhuo; Xu, Xiaogang

doi:10.15537/smj.2016.12.15972

Cited by 69 publications

(42 citation statements)

References 45 publications

(50 reference statements)

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“…When nucleolar stress occurs, the levels of these three proteins increase and the proteins translocate from the nucleus to the cytoplasm ( 12 , 13 ). Nucleolin is the major nucleolar protein of exponentially growing eukaryotic cells, and participates in many modulations including rDNA transcription, RNA metabolism, and ribosome assembly ( 14 ). Nucleophosmin is a highly and ubiquitously expressed protein, and plays crucial roles in ribosome maturation and export, centrosome duplication and cell cycle progression ( 15 ).…”

Section: Resultsmentioning

confidence: 99%

BMH-21 inhibits viability and induces apoptosis by p53-dependent nucleolar stress responses in SKOV3 ovarian cancer cells

Ling

et al. 2017

Oncology Reports

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The nucleolus is a stress sensor associated with cell cycle progression and apoptosis. Studies have shown that nucleolar stress is positively correlated with apoptosis in breast, prostate and lung cancer cells. However, the role and function of nucleolar stress in ovarian cancer has not been reported. In this study, we found that the nucleolar stress inducer BMH-21 inhibited viability of SKOV3 ovarian cancer cells in a dose-dependent manner. Furthermore, BMH-21 induced the expression of nucleolar stress marker proteins (nucleolin, nucleophosmin and fibrillarin) and promoted the nuclear export of these proteins. BMH-21 also decreased MDM2 proto-oncogene expression and increased protein levels of the tumor suppressor p53 and p53 phosphorylated at serine 15 (p-p53-Ser15), which contributed to increased expression of the downstream apoptosis-related protein BCL2 associated X (BAX) and activation of caspase-3. Taken together, these data provide the first reported evidence that induction of p53-dependent nucleolar stress by BMH-21 induces apoptosis in ovarian cancer. Our data suggest that nucleolar stress might be a pathway suitable for targeting in ovarian cancer.

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Section: Resultsmentioning

confidence: 99%

BMH-21 inhibits viability and induces apoptosis by p53-dependent nucleolar stress responses in SKOV3 ovarian cancer cells

Ling

et al. 2017

Oncology Reports

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“…Moreover, nucleolin stabilizes the mRNA of anti-apoptotic protein bcl-2 [ 53 ]. Recent studies have proposed that nucleolin is a novel target for anticancer therapy as demonstrated by the effects of antagonistic molecules [ 33 , 54 , 55 ]. Nucleolin is a multifunctional protein that is mainly found in the nucleolus, but it is also observed in the nucleoplasm and cytoplasm.…”

Section: Discussionmentioning

confidence: 99%

Nucleolin facilitates nuclear retention of an ultraconserved region containing TRA2β4 and accelerates colon cancer cell growth

et al. 2018

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Transcribed-ultraconserved regions (T-UCRs), which contain conserved sequences with 100% identity across human, rat and mouse species, are a novel category of functional RNAs. The human transformer 2β gene (TRA2B) encodes a UCR that spans exon 2 (276 bp) and its neighboring introns. Among five spliced RNA variants (TRA2β1-5) transcribed from the TRA2B gene, only TRA2β4 contains the conserved exon 2. TRA2β4 is overexpressed in colon cancer cells and accelerates cell growth by blocking the transcription of CDKN1A. However, the mechanisms underlying the overexpression of TRA2β4 in colon cancer cells are unknown. Using biotinylated RNA pull-down assays followed by liquid chromatography-mass spectrometric analysis, we identified nucleolin as a TRA2β4-binding protein. Knockdown of nucleolin reduced the nuclear retention of TRA2β4 and accelerated its degradation in the cytoplasm, whereas nucleolin overexpression increased TRA2β4 levels and its mitogenic activity. Nucleolin directly bound to TRA2β4 exon 2 via the glycine/arginine-rich (GAR) domain. Overexpression of GAR-deficient nucleolin failed to increase TRA2β4 expression and growth of colon cancer cells. RNA fluorescence in situ hybridization showed that TRA2β4 co-localized with nucleolin in nuclei but not with the mutant lacking GAR. Our results suggest that specific interactions between nucleolin and UCR-containing TRA2β4 may be associated with abnormal growth of colon cancer cells.

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“…The tumor-targeting ligand in the TDDS is a DNA aptamer (AS1411) that and can bind with nucleolin, which is expressed on the cell surface of colon cancer. 24 DTX is an FDA-approved broad-spectrum anticancer agent that is more potent than paclitaxel. 25 , 26 We now report that Apt-NPs-DTX is more efficacious against colon cancer cells vs non-targeted drug delivery system.…”

Section: Introductionmentioning

confidence: 99%

<p>Targeted Treatment of Colon Cancer with Aptamer-Guided Albumin Nanoparticles Loaded with Docetaxel</p>

Yu¹,

Li²,

Duan³

et al. 2020

IJN

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Purpose Chemotherapy of colon cancer needs improvement to mitigate the severe adverse effects (AEs) associated with the cytotoxic drugs. The aim of this study is to develop a novel targeted drug delivery system (TDDS) with practical application potential for colon cancer treatment. Methods The TDDS was built by loading docetaxel (DTX) in albumin nanoparticles (NPs) that were functionalized with nucleolin-targeted aptamers (AS1411). Results The TDDS (Apt-NPs-DTX) had an average size of 62 nm and was negatively charged with a zeta potential of −31.2 mV. DTX was released from the albumin NP with a typical sustained release profile. Aptamer-guided NPs were preferentially ingested by nucleolin-expressing CT26 colon cancer cells vs the control cells. In vitro cytotoxicity study showed that Apt-NPs-DTX significantly enhanced the killing of CT26 colon cancer cells. Importantly, compared with non-targeted drug delivery, Apt-NPs-DTX treatment significantly improved antitumor efficacy and prolonged the survival of CT26-bearing mice, without raising systemic toxicity. Conclusion The results suggest that Apt-NPs-DTX has potential in the targeted treatment of colon cancer.

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Roles of nucleolin

Cited by 69 publications

References 45 publications

BMH-21 inhibits viability and induces apoptosis by p53-dependent nucleolar stress responses in SKOV3 ovarian cancer cells

BMH-21 inhibits viability and induces apoptosis by p53-dependent nucleolar stress responses in SKOV3 ovarian cancer cells

Nucleolin facilitates nuclear retention of an ultraconserved region containing TRA2β4 and accelerates colon cancer cell growth

<p>Targeted Treatment of Colon Cancer with Aptamer-Guided Albumin Nanoparticles Loaded with Docetaxel</p>

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