The cancer‐related transcription factor RUNX2 modulates expression and secretion of the matricellular protein osteopontin in osteosarcoma cells to promote adhesion to endothelial pulmonary cells and lung metastasis

Villanueva, Francisco; Araya, Héctor; Briceño, Pedro; Varela, Nelson; Stevenson, A.E.; Jerez, Sofía; Tempio, Fabián; Chnaiderman, Jonás; Perez, Carola; Villarroel, Milena; V, Emma Concha; Khani, Farzaneh; Thaler, Roman; Salazar‐Onfray, Flavio; Stein, Gary S.; Wijnen, André J. van; Galindo, Mario

doi:10.1002/jcp.28046

Cited by 41 publications

(34 citation statements)

References 164 publications

(328 reference statements)

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“…Accumulating evidences have confirmed the oncogenic role of RUNX2 in several cancers, and it has also been associated with the prognosis of patients with recurrence and metastasis [42][43][44][45][46]. Therefore, we investigated the potential role of RUNX2 in human CRC.…”

Section: Discussionmentioning

confidence: 98%

RUNX2 interacts with BRG1 to target CD44 for promoting invasion and migration of colorectal cancer cells

et al. 2020

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Background Cancer stem cells (CSCs) play an important role in tumor invasion and metastasis. CD44 is the most commonly used marker of CSCs, with the potential to act as a determinant against the invasion and migration of CSCs and as the key factor in epithelial–mesenchymal transition (EMT)-like changes that occur in colorectal cancer (CRC). Runt-related transcription factor-2 (RUNX2) is a mesenchymal stem marker for cancer that is involved in stem cell biology and tumorigenesis. However, whether RUNX2 is involved in CSC and in inducing EMT-like changes in CRC remains uncertain, warranting further investigation. Methods We evaluated the role of RUNX2 in the invasion and migration of CRC cells as a promoter of CD44-induced stem cell- and EMT-like modifications. For this purpose, western blotting was employed to analyze the expression of differential proteins in CRC cells. We conducted sphere formation, wound healing, and transwell assays to investigate the biological functions of RUNX2 in CRC cells. Cellular immunofluorescence and coimmunoprecipitation (co-IP) assays were performed to study the relationship between RUNX2 and BRG1. Real-time quantitative PCR (RT-qPCR) and immunohistochemistry (IHC) were performed to analyze the expressions of RUNX2, BRG1, and CD44 in the CRC tissues. Results We found that RUNX2 could markedly induce the CRC cell sphere-forming ability and EMT. Interestingly, the RUNX2-mediated EMT in CRC cell may be associated with the activation of CD44. Furthermore, RUNX2 was found to interact with BRG1 to promote the recruitment of RUNX2 to the CD44 promoter. Conclusions Our cumulative findings suggest that RUNX2 and BRG1 can form a compact complex to regulate the transcription and expression of CD44, which has possible involvement in the invasion and migration of CRC cells.

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Section: Discussionmentioning

confidence: 98%

RUNX2 interacts with BRG1 to target CD44 for promoting invasion and migration of colorectal cancer cells

et al. 2020

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“…Mechanically, we confirmed that ZNF521 exerted its effects by regulating Runx2 expression and repressed its transcriptional activity. Runx2 was involved in osteoblastic differentiation, skeletal morphogenesis and cancer progression [23][24][25]. Runx2 overexpression promoted CXCR7 expression and cellular trafficking, AKT hyperactivation and prostate tumorigenesis [26].…”

Section: Discussionmentioning

confidence: 99%

ZNF521 which is downregulated by miR-802 suppresses malignant progression of Hepatocellular Carcinoma through regulating Runx2 expression

Yang¹,

Wang²,

Chen³

et al. 2020

J. Cancer

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Zinc finger protein 521 (ZNF521) plays an important role in the tumor development and process. However, its regulatory role in hepatocellular carcinoma (HCC) remains unclear. In this study, we demonstrated for the first time that ZNF521 mRNA and protein was down-regulated in HCC tissues and cell lines. Down-regulated ZNF521 expression was significantly associated with malignant prognostic features, including advanced TNM stage and large tumor size. For 5-year survival, ZNF521 served as a potential prognostic marker of HCC patients. Moreover, ZNF521 inhibited cell proliferation, colony formation and cell viability through Runx2 transcriptional inhibition and AKT phosphorylation pathway. Moreover, we demonstrated that ZNF521 expression was regulated by miR-802. In HCC tissues. MiR-802 has an inverse correlation with ZNF521 expression. In conclusion, we demonstrate for the first time that ZNF521 is down-regulated in HCC tissues and inhibits HCC growth through Runx2 transcriptional inhibition and AKT inactivation, which was regulated by miR-802, suggesting the potential therapeutic value for HCC.

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“…Rustamov et al established that bone sialoprotein predicts unsatisfactory prognosis in triple-negative breast cancer, while its expression is elevated by RUNX2 [27]. Besides, it has been suggested by Villanueva et al that enhanced RUNX2 might transcriptionally induce gene expression engaged in tumor development and metastasis [28]. More specifically, the conversion from osteopontin A to osteopontin c could be accelerated by RUNX2 through recognizing the gene promoter of osteopontin in NSCLC cells [29].…”

Section: Discussionmentioning

confidence: 99%

The MicroRNA-130a-5p/RUNX2/STK32A Network Modulates Tumor Invasive and Metastatic Potential in Non-Small Cell Lung Cancer

Xie

Lei

et al. 2020

Preprint

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Background Non-small cell lung cancer (NSCLC) remains a huge health burden for human health and life worldwide. Our study here was to illuminate the relevance of microRNA-130a-5p (miR-130a-5p) on growth and epithelial mesenchymal transition (EMT) in NSCLC cells as along with metastasis in vivo, and to explore the underlying mechanism.Methods RT-qPCR was carried out for miR-130a-5p expression determination in NSCLC cells and tissue samples. Dual luciferase reporter gene assay, RT-qPCR and western blot were carried out to study the potential targets of miR-130a-3p. Effects of miR-130a-5p, runt-related transcription factor 2 (RUNX2) and encoding serine/threonine kinase 32A (STK32A) on NSCLC proliferation, migration, invasion as well as EMT processes were assessed by cell counting kits-8, colony formation, Transwell and western blot assays.Results miR-130a-5p was diminished in NSCLC tissues and cells versus their counterparts. miR-130a-5p exerted its repressive role in NSCLC by curtailing cell viability, migration, invasion as well as EMT, while facilitating apoptosis. miR-130a-5p directly targeted RUNX2, a transcription factor, and conversely regulated its expression. RUNX2 was found to interacted with STK32A to promote its expression. Following the validation of the tumor-supporting role of STK32A in NSCLC cells, RUNX2 overexpression was monitored to reverse miR-130a-5p-inhibited NSCLC tumor volume and weight through enhancing STK32A expression in vivo.Conclusions miR-130a-5p diminished the growth and EMT of NSCLC cells by regulating the RUNX2/STK32A axis, offering possible targets for the treatment for NSCLC.

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The cancer‐related transcription factor RUNX2 modulates expression and secretion of the matricellular protein osteopontin in osteosarcoma cells to promote adhesion to endothelial pulmonary cells and lung metastasis

Cited by 41 publications

References 164 publications

RUNX2 interacts with BRG1 to target CD44 for promoting invasion and migration of colorectal cancer cells

RUNX2 interacts with BRG1 to target CD44 for promoting invasion and migration of colorectal cancer cells

ZNF521 which is downregulated by miR-802 suppresses malignant progression of Hepatocellular Carcinoma through regulating Runx2 expression

The MicroRNA-130a-5p/RUNX2/STK32A Network Modulates Tumor Invasive and Metastatic Potential in Non-Small Cell Lung Cancer

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