&lt;p&gt;The oncogenic role of GNL3 in the progression and metastasis of osteosarcoma&lt;/p&gt;

Li, Tianyou; Long, Li; Wu, Xiangyu; Tian, Kaixuan; Wang, Yanzhou

doi:10.2147/cmar.s195360

Cited by 13 publications

(17 citation statements)

References 28 publications

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“…Moreover, the absence of BOP1 was discovered to lead to the activation of MAPK pathway, leading to BRAF inhibitor resistance in melanoma (26). GNL3, as an oncogene, promotes the progression of osteosarcoma by regulating epithelial-mesenchymal transition (EMT) (27). BYSL was found to enhance glioblastoma cell invasion, cell migration, and EMT through the GSK-3β/β-catenin signaling pathway (28).…”

Section: Discussionmentioning

confidence: 99%

Development and validation of a prediction model for lung adenocarcinoma based on RNA-binding protein

et al. 2021

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Background: RNA-binding proteins (RBPs) have been found to participate in the development and progression of cancer. This present study aimed to construct a RBP-based prognostic prediction model for lung adenocarcinoma (LUAD).Methods: RNA sequencing data and corresponding clinical information were acquired from The Cancer Genome Atlas (TCGA) and served as a training set. The prediction model was validated using the dataset in Gene Expression Omnibus (GEO) databases. Univariate and multivariate Cox regression analyses were conducted to identify the RBPs associated with survival. R software (http://www.r-project.org) was used for analysis in this study.Results: Nine hub prognostic RBPs (CIRBP, DARS2, DDX24, GAPDH, LARP6, SNRPE, WDR3, ZC3H12C, ZC3H12D) were identified by univariate Cox regression analysis and multivariate Cox regression analysis. Using a risk score based on the nine-hub RBP model, we separated the LUAD patients into a lowrisk group and a high-risk group. The outcomes revealed that patients in the high-risk group had poorer survival than those in the low-risk group. This signature was validated in the GEO database. Further study revealed that the risk score can be an independent prognostic biomarker for LUAD. A nomogram based on the nine hub RBPs was built to quantitatively predict the prognosis of LUAD patients. Conclusions:Our nine-gene signature model could be used as a marker to predict the prognosis of LUAD and has potential for use in treatment individualization.

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Section: Discussionmentioning

confidence: 99%

Development and validation of a prediction model for lung adenocarcinoma based on RNA-binding protein

et al. 2021

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“…The reduced expression of GNL3 gene, encoding for nucleostemin, is particularly interesting in the context of OC tumors since this protein has been found to have a role in the migration ability and in the epithelial-mesenchymal transition of OC cells [ 30 ]. A dysregulated expression of GNL3 has been observed in several cancer cells and it was found to be associated with forced cell growth and survival, increased propensity to metastasize as well as with enhanced resistance to therapies, relapse and poor prognosis [ 25 , 26 , 27 , 28 , 29 ]. Interestingly, OTX015 and IR combination showed an enhanced effect in reducing the expression of GNL3 protein, this having a potential benefit in counteracting radioresistance mechanisms and so improving the therapeutic efficacy against OC tumors.…”

Section: Discussionmentioning

confidence: 99%

“…Notwithstanding the information about the anticancer effects of different BETi agents, mainly JQ1 drug, in OC [ 20 , 21 , 22 , 23 ], it is useful to investigate their molecular mechanisms and their precise targeted factors both as monotherapies and combined with conventional treatments. Our recent observations have linked OTX015 antitumor activity to a marked downregulation of GNL3 gene [ 11 ], coding for the G nucleolar 3 protein (often indicated as nucleostemin) that is implied in growth, survival, genome stability and stemness capacities of various cancer cell types [ 24 ], this being also related with cancer resistance to conventional treatments [ 24 , 25 , 26 , 27 , 28 ]. Currently, only few studies have correlated the aberrant expression of GNL3 gene with OC tumorigenesis [ 29 , 30 ].…”

Section: Introductionmentioning

confidence: 99%

OTX015 Epi-Drug Exerts Antitumor Effects in Ovarian Cancer Cells by Blocking GNL3-Mediated Radioresistance Mechanisms: Cellular, Molecular and Computational Evidence

Megiorni

Camero

Pontecorvi

et al. 2021

Cancers

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Ovarian cancer (OC) is the most aggressive gynecological tumor worldwide and, notwithstanding the increment in conventional treatments, many resistance mechanisms arise, this leading to cure failure and patient death. So, the use of novel adjuvant drugs able to counteract these pathways is urgently needed to improve patient overall survival. A growing interest is focused on epigenetic drugs for cancer therapy, such as Bromodomain and Extra-Terminal motif inhibitors (BETi). Here, we investigate the antitumor effects of OTX015, a novel BETi, as a single agent or in combination with ionizing radiation (IR) in OC cellular models. OTX015 treatment significantly reduced tumor cell proliferation by triggering cell cycle arrest and apoptosis that were linked to nucleolar stress and DNA damage. OTX015 impaired migration capacity and potentiated IR effects by reducing the expression of different drivers of cancer resistance mechanisms, including GNL3 gene, whose expression was found to be significantly higher in OC biopsies than in normal ovarian tissues. Gene specific knocking down and computational network analysis confirmed the centrality of GNL3 in OTX015-mediated OC antitumor effects. Altogether, our findings suggest OTX015 as an effective option to improve therapeutic strategies and overcome the development of resistant cancer cells in patients with OC.

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“…GNL3 interacts with p53 and MDM2 and thus influences the cell cycle progression and cellular differentiation, with a decrease in GNL3 (Figure 8B) [44,45]. GNL3 also inhibits proliferation of several tumor cells [46,47].…”

Section: Discussionmentioning

confidence: 99%

Identification of Binding Proteins for TSC22D1 Family Proteins Using Mass Spectrometry

Kamimura

Uchida

Kanno

et al. 2021

IJMS

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TSC-22 (TGF-β stimulated clone-22) has been reported to induce differentiation, growth inhibition, and apoptosis in various cells. TSC-22 is a member of a family in which many proteins are produced from four different family genes. TSC-22 (corresponding to TSC22D1-2) is composed of 144 amino acids translated from a short variant mRNA of the TSC22D1 gene. In this study, we attempted to determine the intracellular localizations of the TSC22D1 family proteins (TSC22D1-1, TSC-22 (TSC22D1-2), and TSC22(86) (TSC22D1-3)) and identify the binding proteins for TSC22D1 family proteins by mass spectrometry. We determined that TSC22D1-1 was mostly localized in the nucleus, TSC-22 (TSC22D1-2) was localized in the cytoplasm, mainly in the mitochondria and translocated from the cytoplasm to the nucleus after DNA damage, and TSC22(86) (TSC22D1-3) was localized in both the cytoplasm and nucleus. We identified multiple candidates of binding proteins for TSC22D1 family proteins in in vitro pull-down assays and in vivo binding assays. Histone H1 bound to TSC-22 (TSC22D1-2) or TSC22(86) (TSC22D1-3) in the nucleus. Guanine nucleotide-binding protein-like 3 (GNL3), which is also known as nucleostemin, bound to TSC-22 (TSC22D1-2) in the nucleus. Further investigation of the interaction of the candidate binding proteins with TSC22D1 family proteins would clarify the biological roles of TSC22D1 family proteins in several cell systems.

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<p>The oncogenic role of GNL3 in the progression and metastasis of osteosarcoma</p>

Cited by 13 publications

References 28 publications

Development and validation of a prediction model for lung adenocarcinoma based on RNA-binding protein

Development and validation of a prediction model for lung adenocarcinoma based on RNA-binding protein

OTX015 Epi-Drug Exerts Antitumor Effects in Ovarian Cancer Cells by Blocking GNL3-Mediated Radioresistance Mechanisms: Cellular, Molecular and Computational Evidence

Identification of Binding Proteins for TSC22D1 Family Proteins Using Mass Spectrometry

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