Expression of <scp>FBXW11</scp> in normal and disease‐associated osteogenic cells

Carbonare, Luca Dalle; Gomez-Lira, Macarena; Minoia, Arianna; Bertacco, Jessica; Orsi, Silvia; Lauriola, Angela; Vigni, Veronica Li; Gandini, A.; Antoniazzi, Franco; Zipeto, Donato; Mottes, Monica; Bhandary, Lekhana; Guardavaccaro, Daniele; Valenti, Maria Teresa

doi:10.1111/jcmm.17767

Cited by 5 publications

(5 citation statements)

References 45 publications

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“…Transfection of the RUNX2-expressing plasmid was carried out using RUNX2 Lenti ORF particles from Origene Technologies (Rockville, MD, USA), following the manufacturer’s instructions. RUNX2 KO cells were grown to 70% confluence and subsequently transfected with 1.3 µg/mL or 2.6 µg/mL RUNX2-expressing pcDNA3 vector, using the Lipofectamine 3000 reagent (Thermo Fisher Scientific, Waltham, MA, USA; reference: L3000-008), as we previously reported [ 17 ].…”

Section: Methodsmentioning

confidence: 99%

“…Total RNA extraction and reverse transcription (RT) were performed using previously reported methods [ 17 ]. Briefly, cells were harvested and total RNA was isolated using the RNeasy ® protect mini kit (Qiagen, Hilden, Germany), according to the manufacturer’s instructions.…”

Section: Methodsmentioning

confidence: 99%

“…The thermal cycling conditions included an initial denaturation step followed by 40 amplification cycles, as previously reported [ 17 ]. The fluorescence signal was captured and analysed using a real-time PCR system.…”

Section: Methodsmentioning

confidence: 99%

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Exploring the Interplay of RUNX2 and CXCR4 in Melanoma Progression

Dalle Carbonare,

Minoia,

Vareschi

et al. 2024

Cells

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Overexpression of the Runt-related transcription factor 2 (RUNX2) has been reported in several cancer types, and the C-X-C motif chemokine receptor 4 (CXCR4) has an important role in tumour progression. However, the interplay between CXCR4 and RUNX2 in melanoma cells remains poorly understood. In the present study, we used melanoma cells and a RUNX2 knockout (RUNX2-KO) in vitro model to assess the influence of RUNX2 on CXCR4 protein levels along with its effects on markers associated with cell invasion and autophagy. Osteotropism was assessed using a 3D microfluidic model. Moreover, we assessed the impact of CXCR4 on the cellular levels of key cellular signalling proteins involved in autophagy. We observed that melanoma cells express both RUNX2 and CXCR4. Restored RUNX2 expression in RUNX2 KO cells increased the expression levels of CXCR4 and proteins associated with the metastatic process. The protein markers of autophagy LC3 and beclin were upregulated in response to increased CXCR4 levels. The CXCR4 inhibitor WZ811 reduced osteotropism and activated the mTOR and p70-S6 cell signalling proteins. Our data indicate that the RUNX2 transcription factor promotes the expression of the CXCR4 chemokine receptor on melanoma cells, which in turn promotes autophagy, cell invasiveness, and osteotropism, through the inhibition of the mTOR signalling pathway. Our data suggest that RUNX2 promotes melanoma progression by upregulating CXCR4, and we identify the latter as a key player in melanoma-related osteotropism.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Exploring the Interplay of RUNX2 and CXCR4 in Melanoma Progression

Dalle Carbonare,

Minoia,

Vareschi

et al. 2024

Cells

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“…The ubiquitin-proteasome system, which degrades various key regulatory proteins, is crucial for cellular homeostasis. FBXW11 regulates cell proliferation by targeting proteins involved in the cell cycle or those degraded by this system, influencing animal development [21]. Schierding et al's GWAS analysis identified FBXW11 as a crucial modifier of growth, functioning within the regulatory network [22].…”

Section: Genes Associated With the Growthmentioning

confidence: 99%

Whole-Genome Resequencing Revealed Selective Signatures for Growth Traits in Hu and Gangba Sheep

Yang,

Shang,

Bao

et al. 2024

Genes

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A genomic study was conducted to uncover the selection signatures in sheep that show extremely significant differences in growth traits under the same breed, age in months, nutrition level, and management practices. Hu sheep from Gansu Province and Gangba sheep from the Tibet Autonomous Region in China were selected. We collected whole-genome data from 40 sheep individuals (24 Hu sheep and 16 Gangba sheep), through whole-genome sequencing. Selection signals were analyzed using parameters such as FST, π ratio, and Tajima’s D. We have identified several candidate genes that have undergone strong selection, particularly those associated with growth traits. Specifically, five growth-related genes were identified in both the Hu sheep group (HDAC1, MYH7B, LCK, ACVR1, GNAI2) and the Gangba sheep group (RBBP8, ACSL3, FBXW11, PLAT, CRB1). Additionally, in a genomic region strongly selected in both the Hu and Gangba sheep groups (Chr 22: 51,425,001-51,500,000), the growth-associated gene CYP2E1 was identified, further highlighting the genetic factors influencing growth characteristics in these breeds. This study analyzes the genetic basis for significant differences in sheep phenotypes, identifies candidate genes related to sheep growth traits, lays the foundation for molecular genetic breeding in sheep, and accelerates the genetic improvement in livestock.

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“…Differential expression analysis showed 12 downregulated genes (mostly associated with the negative regulation of transcription: NFKBIB , BTRC , CREBBP , HDAC1 , NCOR2 , and FBXW11 ) and 19 upregulated genes [mostly associated with protein ubiquitination ( SOCS1 , RBX1 , RPS27A , UBB , UBA52 , and UBE2N ), positive regulation of cell proliferation ( CTNNB1 , NRAS , HRAS , CDKN1A , and STAT3 ), and cell surface receptor signaling pathways ( IL6 , IFNA5 , IFNA7 , IFNA16 , and NGF ) in OS samples compared to controls. Several of these genes have already been associated with OS pathophysiology [ 149 , 163 , 164 , 165 , 166 , 167 , 168 , 169 , 170 , 171 , 172 , 173 , 174 , 175 , 176 , 177 ]. Moreover, KEGG functional enrichment was assessed through STRING v12 (available at accessed on 17 April 2024) and showed that under-expressed genes belonged mainly to MAPK and WNT signaling pathways, while upregulated genes belonged to the PI3K/AKT and JAK/STAT cascades ( Figure 6 C), reinforcing the concept of NF-κB as a common player underneath OS establishment and progression.…”

Section: Nf-κb Dysregulation and Cancermentioning

confidence: 99%

Amicis Omnia Sunt Communia: NF-κB Inhibition as an Alternative to Overcome Osteosarcoma Heterogeneity

Medeiros,

Guenka,

Bastos

et al. 2024

Pharmaceuticals

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Tumor heterogeneity poses a significant challenge in osteosarcoma (OS) treatment. In this regard, the “omics” era has constantly expanded our understanding of biomarkers and altered signaling pathways (i.e., PI3K/AKT/mTOR, WNT/β-catenin, NOTCH, SHH/GLI, among others) involved in OS pathophysiology. Despite different players and complexities, many commonalities have been described, among which the nuclear factor kappa B (NF-κB) stands out. Its altered activation is pervasive in cancer, with pleiotropic action on many disease-relevant traits. Thus, in the scope of this article, we highlight the evidence of NF-κB dysregulation in OS and its integration with other cancer-related pathways while we summarize the repertoire of compounds that have been described to interfere with its action. In silico strategies were used to demonstrate that NF-κB is closely coordinated with other commonly dysregulated signaling pathways not only by functionally interacting with several of their members but also by actively participating in the regulation of their transcription. While existing inhibitors lack selectivity or act indirectly, the therapeutic potential of targeting NF-κB is indisputable, first for its multifunctionality on most cancer hallmarks, and secondly, because, as a common downstream effector of the many dysregulated pathways influencing OS aggressiveness, it turns complex regulatory networks into a simpler picture underneath molecular heterogeneity.

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Expression of FBXW11 in normal and disease‐associated osteogenic cells

Cited by 5 publications

References 45 publications

Exploring the Interplay of RUNX2 and CXCR4 in Melanoma Progression

Exploring the Interplay of RUNX2 and CXCR4 in Melanoma Progression

Whole-Genome Resequencing Revealed Selective Signatures for Growth Traits in Hu and Gangba Sheep

Amicis Omnia Sunt Communia: NF-κB Inhibition as an Alternative to Overcome Osteosarcoma Heterogeneity

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