A Potential Role of RUNX2- RUNT Domain in Modulating the Expression of Genes Involved in Bone Metastases: An In Vitro Study with Melanoma Cells

Deiana, Michela; Carbonare, Luca Dalle; Serena, Michela; Cheri, Samuele; Mutascio, Simona; Gandini, A.; Innamorati, Giulio; Lorenzi, Pamela; Cumerlato, Michela; Bertacco, Jessica; Antoniazzi, Franco; Mottes, Monica; Valenti, Maria Teresa

doi:10.3390/cells9030751

Cited by 8 publications

(15 citation statements)

References 46 publications

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“… 66 RUNT domain promotes bone metastasis of melanoma cells through the complex interactions with genes involved in bone remodeling through the ERK/p-ERK and AKT/p-AKT pathways. 67 All these findings indicate that the RUNT domain is involved in melanoma metastasis and cell migration. RUNX2 can reactivate the MAPK and PI3K/AKT pathways, thereby endowing melanoma cells with high metastatic potential.…”

Section: The Transcription Factor Runx2 and Malignant Tumorsmentioning

confidence: 93%

RUNX2 as a promising therapeutic target for malignant tumors

Zhao

Yang

Chai

et al. 2021

CMAR

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The transcription factor runt-related protein 2 (RUNX2) has an important impact on the transformation of bone marrow mesenchymal stem cells to osteoblasts. Further studies have shown that RUNX2 plays a key role in the invasion and metastasis of cancers. RUNX2 is a “key” molecule in the regulatory network comprised of multiple signaling pathways upstream and its target downstream molecules. Due to the complex regulatory mechanisms of RUNX2, the specific mechanism underlying the occurrence, development and prognosis of malignant tumors has not been fully understood. Currently, RUNX2 as a promising therapeutic target for cancers has become a research hotspot. Herein, we reviewed the current literature on the modulatory functions and mechanisms of RUNX2 in the development of malignant tumors, aiming to explore its potential clinical application in the diagnosis, prognosis and treatment of tumors.

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Section: The Transcription Factor Runx2 and Malignant Tumorsmentioning

confidence: 93%

RUNX2 as a promising therapeutic target for malignant tumors

Zhao

Yang

Chai

et al. 2021

CMAR

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“…The ten most enriched known motifs identified by HOMER software are listed in Figure 4B . Among these enriched motifs, Runx2 was of particular interest because substantial in vivo and in vitro studies have shown that this gene is strongly associated with osteogenesis ( Tosa et al, 2019 ; Deiana et al, 2020 ). This suggested that Dlx2 may function in collaboration with Runx2 to reshape the transcriptome when Dlx2 is overexpressed.…”

Section: Resultsmentioning

confidence: 99%

Effects of Dlx2 overexpression on the genes associated with the maxillary process in the early mouse embryo

et al. 2023

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The transcription factor Dlx2 plays an important role in craniomaxillofacial development. Overexpression or null mutations of Dlx2 can lead to craniomaxillofacial malformation in mice. However, the transcriptional regulatory effects of Dlx2 during craniomaxillofacial development remain to be elucidated. Using a mouse model that stably overexpresses Dlx2 in neural crest cells, we comprehensively characterized the effects of Dlx2 overexpression on the early development of maxillary processes in mice by conducting bulk RNA-Seq, scRNA-Seq and CUT&Tag analyses. Bulk RNA-Seq results showed that the overexpression of Dlx2 resulted in substantial transcriptome changes in E10.5 maxillary prominences, with genes involved in RNA metabolism and neuronal development most significantly affected. The scRNA-Seq analysis suggests that overexpression of Dlx2 did not change the differentiation trajectory of mesenchymal cells during this development process. Rather, it restricted cell proliferation and caused precocious differentiation, which may contribute to the defects in craniomaxillofacial development. Moreover, the CUT&Tag analysis using DLX2 antibody revealed enrichment of MNT and Runx2 motifs at the putative DLX2 binding sites, suggesting they may play critical roles in mediating the transcriptional regulatory effects of Dlx2. Together, these results provide important insights for understanding the transcriptional regulatory network of Dlx2 during craniofacial development.

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“…RUNX2 can also be regulated post‐transcriptionally and we recently demonstrated that RUNX2 protein levels are increased in miR‐204‐silenced MSCs during the middle phase of osteogenic differentiation 17 . Moreover, using melanoma cells KO for the RUNT domain of RUNX2, we demonstrated that the RUNT domain plays an important role in the modulation of the expression of genes involved in bone metastases 18 …”

Section: Introductionmentioning

confidence: 85%

“…17 Moreover, using melanoma cells KO for the RUNT domain of RUNX2, we demonstrated that the RUNT domain plays an important role in the modulation of the expression of genes involved in bone metastases. 18 The present work, therefore, contributes to the understanding of FBXW11 role in osteogenic cells by evaluating its modulation both during osteogenic commitment and in altered osteoblastic cells characterized by RUNX2 mutations or resulting from tumour transformation.…”

mentioning

confidence: 94%

Expression of FBXW11 in normal and disease‐associated osteogenic cells

Carbonare

Gomez-Lira

Minoia

et al. 2023

J Cellular Molecular Medi

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The ubiquitin‐proteasome system (UPS) plays an important role in maintaining cellular homeostasis by degrading a multitude of key regulatory proteins. FBXW11, also known as b‐TrCP2, belongs to the F‐box family, which targets the proteins to be degraded by UPS. Transcription factors or proteins associated with cell cycle can be modulated by FBXW11, which may stimulate or inhibit cellular proliferation. Although FBXW11 has been investigated in embryogenesis and cancer, its expression has not been evaluated in osteogenic cells. With the aim to explore FBXW11gene expression modulation in the osteogenic lineage we performed molecular investigations in mesenchymal stem cells (MSCs) and osteogenic cells in normal and pathological conditions. In vitro experiments as well as ex vivo investigations have been performed. In particular, we explored the FBXW11 expression in normal osteogenic cells as well as in cells of cleidocranial dysplasia (CCD) patients or osteosarcoma cells. Our data showed that FBXW11 expression is modulated during osteogenesis and overexpressed in circulating MSCs and in osteogenically stimulated cells of CCD patients. In addition, FBXW11 is post‐transcriptionally regulated in osteosarcoma cells leading to increased levels of beta‐catenin. In conclusion, our findings show the modulation of FBXW11 in osteogenic lineage and its dysregulation in impaired osteogenic cells.

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A Potential Role of RUNX2- RUNT Domain in Modulating the Expression of Genes Involved in Bone Metastases: An In Vitro Study with Melanoma Cells

Cited by 8 publications

References 46 publications

RUNX2 as a promising therapeutic target for malignant tumors

RUNX2 as a promising therapeutic target for malignant tumors

Effects of Dlx2 overexpression on the genes associated with the maxillary process in the early mouse embryo

Expression of FBXW11 in normal and disease‐associated osteogenic cells

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