Deciphering signaling networks in osteosarcoma pathobiology

Adamopoulos, Christos; Gargalionis, Antonios N.; Basdra, Efthimia K.; Papavassiliou, Athanasios G.

doi:10.1177/1535370216648806

Cited by 43 publications

(38 citation statements)

References 88 publications

(152 reference statements)

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“…The functions of most of these molecules and pathways in bone development and disease have been studied in detail [73, 92-100]. Results from these completed trials, as well as from studies evaluating other types of treatments such as immunotherapy, have been reviewed recently and will not be described here [9, 101-105]. In general, the findings from these targeted therapy trials have been unsatisfactory.…”

Section: Driver-dependent Genetic Vulnerabilities As Targets Of Osmentioning

confidence: 99%

Molecular genetics of osteosarcoma

Rickel

Fang

Tao

2017

Bone

206

179

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Osteosarcoma is the predominant form of bone cancer, affecting mostly adolescents. Recent progress made in molecular genetic studies of osteosarcoma has changed our view on the cause of the disease and ongoing therapeutic approaches for patients. As we draw closer to gaining more complete catalogues of candidate cancer driver genes in common forms of cancer, the landscape of somatic mutations in osteosarcoma is emerging from its first phase. In this review, we summarize recent whole genome and/or whole exome genomic studies, and then put these findings in the context of genetic hallmarks of somatic mutations and mutational processes in human osteosarcoma. One of the lessons learned here is that the extent of somatic mutations and complexity of the osteosarcoma genome are similar to that of common forms of adult cancer. Thus, a much higher number of samples than those currently obtained are needed to complete the catalogue of driver mutations in human osteosarcoma. In parallel, genetic studies in other species have revealed candidate driver genes and their roles in the genesis of osteosarcoma. This review also summarizes newly identified drivers in genetically engineered mouse models (GEMMs) and discusses our understanding of the impact of nature and number of drivers on tumor latency, subtypes, and metastatic potentials of osteosarcoma. It is becoming apparent that a synergistic team composed of three drivers (one ‘first driver’ and two ‘synergistic drivers’) may be required to generate an animal model that recapitulates aggressive osteosarcoma with a short latency. Finally, new cancer therapies are urgently needed to improve survival rate and quality of life for osteosarcoma patients. Several vulnerabilities in osteosarcoma are illustrated in this review to exemplify the opportunities for next generation molecularly targeted therapies. However, much work remains in order to complete our understanding of the somatic mutation basis of osteosarcoma, to develop reliable animal models of human disease, and to apply this information to guide new therapeutic approaches for reducing morbidity and mortality of this rare disease.

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Section: Driver-dependent Genetic Vulnerabilities As Targets Of Osmentioning

confidence: 99%

Molecular genetics of osteosarcoma

Rickel

Fang

Tao

2017

Bone

206

179

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“…The phosphatidylinositol 3-kinase PI3K/Akt pathway is considered one of the most critical pathways in osteosarcoma pathogenesis regulating osteosarcoma cell proliferation, invasion, metastasis, and drug sensitivity or resistance [84,85].…”

Section: Lncrnas and Signal Transduction Pathways In Osteosarcomamentioning

confidence: 99%

“…MALAT-1 also acts through the PI3K/Akt pathway to promote osteosarcoma cell proliferation, migration, invasion, and pulmonary metastasis. Furthermore, MALAT-1 knockdown or siRNA interference experiments, carried out by Dong et al and Cai et al, respectively, showed that MALAT1 inhibition suppressed osteosarcoma cell proliferation and metastasis via the PI3K/Akt and RhoA/ROCK signaling pathways by modulating the expression of MMP-9 metalloproteinase [85,87,88]. MALAT-1 is highly expressed in osteosarcoma tissue samples and is correlated with metastatic dissemination and advanced clinical stage [142,143].…”

Section: Lncrnas and Invasion/metastasis In Osteosarcomamentioning

confidence: 99%

Long Noncoding RNAs in Osteosarcoma: Mechanisms and Potential Clinical Implications

Valavanis¹,

Stanc²

2019

Osteosarcoma – Diagnosis, Mechanisms, and Translational Developments

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Long noncoding RNAs (lncRNAs) are noncoding transcripts consisting of a diverse class of long RNAs of more than 200 nucleotides in length. Recent studies have shown that lncRNAs are involved in cell signal transduction pathways, cell cycle and cell death regulation, chromatin remodeling, and gene expression regulation at the transcriptional and posttranscriptional levels. They are also involved in the metastatic process of different types of tumors, such as urothelial carcinoma, colon carcinoma, breast carcinoma, lung carcinoma, and hepatocellular carcinoma. In addition, lncRNAs demonstrate precise expression patterns in specific tissues and cells and therefore play important roles in cell differentiation and tissue development. In this chapter, we review the molecular mechanisms of lncRNA cell functions and their involvement in the pathogenesis, progression, and metastasis of osteosarcoma, a rare bone tumor of childhood and adolescence. We also review emerging clinical implications of lncRNA use as potential prognostic biomarkers and therapeutic targets, as well as their putative involvement in drug resistance, in osteosarcoma progression, and in therapeutic interventions.

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“…3 Molecular alterations in coding RNA-or noncoding RNA (ncRNA)-mediated key signalling pathways are pivotal for tumour progression in osteosarcoma pathogenesis, including cell growth, metastasis, and invasion. 4,5 As such, recognizing the target molecules may provide new diagnosis and treatment regimens for osteosarcoma cases.…”

Section: Introductionmentioning

confidence: 99%

LncRNA DLEU2 promotes tumour growth by sponging miR‐337‐3p in human osteosarcoma

Liu

et al. 2020

Cell Biochemistry & Function

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According to statistics, abnormal regulation of lncRNAs pivotally influences multiple malignant tumours. DLEU2, as one of these lncRNAs, is detected to be related to growth and development of tumours. The molecular mechanisms of DLEU2 in osteosarcoma, however, are still unknown. QRT-PCR was adopted to analyse the correlations of clinicopathological features and prognosis of osteosarcoma cases with DLEU2. The influences of DLEU2 on cell migration and viability were evaluated independently by experiments in vitro and in vivo. Bioinformatics analysis, RNA immunoprecipitation (RIP) assay, and dual luciferase reporter gene assay confirmed the specific binding of DLEU2 to miR-337-3p. Moreover, rescue experiments were carried out to further evaluate the regulatory association between miR-337-3p expression and DLEU2. In osteosarcoma tissues and cells, DLEU2 expression level was raised remarkably in comparison with that in para-carcinoma normal tissues, and DLEU2 high expression had associations with poor prognosis, tumour stages, and TS of osteosarcoma cases. Cell migration ability and viability were blocked by DLEU2 knockdown but enhanced by ectopic DLEU2 expression in vitro and in vivo. Additionally, DLEU2 was found to sponge miR-337-3p and trigger the stimulating effect in osteosarcoma cells, which would be suppressed by miR-337-3p mimics. Furthermore, a negative correlation existed between miR-337-3p expression and DLEU2 in osteosarcoma tissues. This study manifests that DLEU2 sponges miR-337-3p to accelerate tumour growth and is confirmed to be a factor for poor prognosis of osteosarcoma cases. Significance of the Study: LncRNA DLEU2 has been reported to be dysregulated in many tumours; however, the functions and underlying mechanism of DLEU2 in osteosarcoma pathogenesis are still unknown. This study is the first to demonstrate the roles of DLEU2 in osteosarcoma and revealed that DLEU2 may serve as a ceRNA to sponge miR-337-3p and then promote the progression of osteosarcoma, providing a potential therapeutic target for osteosarcoma.

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Deciphering signaling networks in osteosarcoma pathobiology

Cited by 43 publications

References 88 publications

Molecular genetics of osteosarcoma

Molecular genetics of osteosarcoma

Long Noncoding RNAs in Osteosarcoma: Mechanisms and Potential Clinical Implications

LncRNA DLEU2 promotes tumour growth by sponging miR‐337‐3p in human osteosarcoma

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