miRNA-7 and miRNA-324-5p regulate alpha9-Integrin expression and exert anti-oncogenic effects in rhabdomyosarcoma

Molist, Carla; Navarro, Natalia; Giralt, Irina; Zarzosa, Patricia; Gallo-Oller, Gabriel; Pons, Guillem; Magdaleno, Ainara; Moreno, Lucas; Guillén, Gabriela; Hladun, Raquel; Garrido, Marta; Soriano, Aroa; Segura, Miguel F.; Toledo, Josep Sánchez de; Gallego, Soledad; Roma, Josep

doi:10.1016/j.canlet.2020.02.035

Cited by 24 publications

(22 citation statements)

References 32 publications

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“…MicroRNAs (miRNAs/miRs) are a class of small non-coding RNAs (18-25 nucleotides in length) that act as post-transcriptional regulators of gene expression by direct binding to the 3' untranslated regions (3'UTRs) of target mRNAs; this binding induces mRNA degradation and/or translational repression (4). miRNAs participate in a number of biological processes, such as cell cycle progression, proliferation, invasion, migration and cell metabolism (5)(6)(7)(8). The regulatory role of miR-592 is context-dependent.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‑592 promotes cell proliferation, migration and invasion in colorectal cancer by directly targeting SPARC

et al. 2021

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Colorectal cancer (CRC), one of the most common cancer types, causes a large number of cancer-related mortalities annually worldwide. Dysregulated microRNAs (miRNAs/miR) are closely associated with the malignant progression of CRC. Therefore, the present study aimed to investigate the expression and regulatory role of miR-592 in CRC. It was found that miR-592 expression was significantly elevated in CRC tissues and cell lines, and was associated with the prognosis of patients. Cellular phenotype assays demonstrated that miR-592 could promote CRC cell proliferation, migration and invasion. Bioinformatics analysis demonstrated that miR-592 mainly participated in the positive regulation of transcription, as well as the regulation of cell motility. Moreover, miR-592 targets were enriched in several signaling pathways, such as the 'mTOR' and 'FoxO' signaling pathways. In addition, secreted protein acidic and rich in cysteine (SPARC) was identified as a target of miR-592 in CRC. The present results suggested that miR-592 acts as an oncogene in CRC, in part, by directly inhibiting SPARC expression. Collectively, the present study provides a novel potential therapeutic strategy for CRC.

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Section: Introductionmentioning

confidence: 99%

MicroRNA‑592 promotes cell proliferation, migration and invasion in colorectal cancer by directly targeting SPARC

et al. 2021

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“…Hsa-miR-324-5p, which is in another novel regulatory axis we constructed, was considered to be involved in the regulation of ACE1, which enioy the capability of DNA repair and redox regulation [33] , but its role in pathogenesis of OS was not elucidated [58] . And Molist et al found that overexpression of hsa-miR-324-5p could make impairment of cell proliferation and reduce tumor growth in rhabdomyosarcoma [59] . Therefore, it is worth to study the potential functions of hsa-miR-324-5p in OS.…”

Section: Discussionmentioning

confidence: 99%

Identification of the Key Serum Biomarkers to Diagnose and Predict Metastasis of Osteosarcoma Based on the Analysis of Immune Cell Infiltration Characteristics

Chen

et al. 2021

Preprint

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Background: The potential functions of circular RNAs (circRNAs) and micro RNAs (miRNAs) in osteosarcoma (OS) have not been fully elucidated. Especially, the behavior and mechanism of immune responses in OS development and progression have not been fully demonstrated. It was reported that circRNAs and miRNAs can serve as biomarkers for the diagnosis, prognosis, and therapy of many cancers. This study aimed to identify novel key serum biomarkers to diagnose and predict metastasis of OS based on the analysis of immune cell infiltration characteristics.Methods: The differentially-expressed circRNAs (DEcircRNAs), differentially-expressed miRNAs (DEmiRNAs),and differentially-expressed mRNAs (DEmRNAs) of human OS were investigated based on the microarray data downloaded from Gene Expression Omnibus (GEO) datasets. Then, we analyzed immune characteristics pattern of tumor-infiltrating immune cells in OS. On this basis, we identified statistically-significant transcription factors and performed pathway enrichment analysis. Subsequently, we constructed protein-protein interaction (PPI) and competitive endogenous RNA (ceRNA) networks. Moreover, the biological characteristic of targets in ceRNA networks was proposed. Finally, the expression and diagnostic capability of these potential biomarkers from ceRNA network were confirmed by RT-qPCR in patients’ serum.Results: Seven differentially-expressed circRNAs (DEcircRNAs), 166 differentially-expressed miRNAs (DEmiRNAs) and 175 differentially-expressed mRNAs (DEmRNAs) were identified in total. The highest level of infiltration in OS patients were M0 macrophages, M2 macrophages and CD8+ T cells. Further, M0 macrophages and CD8+ T cells were showed the largest negative correlation coefficients. These significant immune characteristics pattern of tumor-infiltrating immune cells were revealed by the principal component analysis in OS. Moreover, we found 185 statistically-significant transcription factors in which the main significant molecules show the potential in immunotherapy of OS. Hsa-circ-0010220, hsa-miR-326, hsa-miR-338-3p, and FAM98A from ceRNA networks associated with immune cell infiltration were confirmed as the potential novel biomarkers for OS diagnosis, of which FAM98A could distinguish and predict metastasis. Most importantly, a novel diagnostic model consisting of the four promising biomarkers (hsa-circ-0010220, hsa-miR-326, hsa-miR-338-3p, and FAM98A) was highlighted with 0.928 AUC value.Conclusions: In summary, the potenial serum biomarkers to diagnose and predict metastasis of OS based on the analysis of immune cell infiltration characteristics were found, and a novel diagnostic model consisting of four promising serum biomarkers was proposed firstly. These results provided a new perspective for the immunotherapy of OS.

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“…Invasion assay was performed as previously described in detail [ 40 ]. Briefly, 1 × 10 5 RD or CW9019 cells were seeded in an 8 μm pore size transwell (Corning), previously coated with 25 µL of BD Matrigel™ (Corning).…”

Section: Methodsmentioning

confidence: 99%

“…At the end of the experiment, the lungs were enzymatically dissociated with collagenase A (Sigma, Saint louis, MO, USA) and analyzed by FACS (FacsAria, BD Bioscience, Franklin Lakes, NJ, USA). Analyses were carried out as previously described [ 40 ]. All procedures were approved by the Ethics Committee of Animal Experimentation of the Vall d’Hebron Research Institute (CEEA 30/14) and were in line with EU directive 2010/63/EU.…”

Section: Methodsmentioning

confidence: 99%

Dickkopf-1 Inhibition Reactivates Wnt/β-Catenin Signaling in Rhabdomyosarcoma, Induces Myogenic Markers In Vitro and Impairs Tumor Cell Survival In Vivo

Giralt

Gallo-Oller

Navarro

et al. 2021

IJMS

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The Wnt/β-catenin signaling pathway plays a pivotal role during embryogenesis and its deregulation is a key mechanism in the origin and progression of several tumors. Wnt antagonists have been described as key modulators of Wnt/β-catenin signaling in cancer, with Dickkopf-1 (DKK-1) being the most studied member of the DKK family. Although the therapeutic potential of DKK-1 inhibition has been evaluated in several diseases and malignancies, little is known in pediatric tumors. Only a few works have studied the genetic inhibition and function of DKK-1 in rhabdomyosarcoma. Here, for the first time, we report the analysis of the therapeutic potential of DKK-1 pharmaceutical inhibition in rhabdomyosarcoma, the most common soft tissue sarcoma in children. We performed DKK-1 inhibition via shRNA technology and via the chemical inhibitor WAY-2626211. Its inhibition led to β-catenin activation and the modulation of focal adhesion kinase (FAK), with positive effects on in vitro expression of myogenic markers and a reduction in proliferation and invasion. In addition, WAY-262611 was able to impair survival of tumor cells in vivo. Therefore, DKK-1 could constitute a molecular target, which could lead to novel therapeutic strategies in RMS, especially in those patients with high DKK-1 expression.

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miRNA-7 and miRNA-324-5p regulate alpha9-Integrin expression and exert anti-oncogenic effects in rhabdomyosarcoma

Cited by 24 publications

References 32 publications

MicroRNA‑592 promotes cell proliferation, migration and invasion in colorectal cancer by directly targeting SPARC

MicroRNA‑592 promotes cell proliferation, migration and invasion in colorectal cancer by directly targeting SPARC

Identification of the Key Serum Biomarkers to Diagnose and Predict Metastasis of Osteosarcoma Based on the Analysis of Immune Cell Infiltration Characteristics

Dickkopf-1 Inhibition Reactivates Wnt/β-Catenin Signaling in Rhabdomyosarcoma, Induces Myogenic Markers In Vitro and Impairs Tumor Cell Survival In Vivo

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