The canonical Wnt-beta-catenin pathway in development and chemotherapy of osteosarcoma

Liu, Chengjun; Shi, Xin E.; Zhou, Guangxin; Liu, Xiaozhou; Wu, Sujia; Zhao, Jianning

doi:10.2741/4187

Cited by 27 publications

(3 citation statements)

References 54 publications

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“…The functional role of the Wnt signaling pathway in OS is not completely understood ( 23 ). A number of studies support the idea that the Wnt signaling pathway serves an anti-tumorigenic effect in OS ( 24 – 26 ), whereas other studies suggest that aberrant activation of the canonical Wnt signaling pathway serves an important role in OS initiation, maintenance and resistance to chemotherapy ( 27 , 28 ). In addition, a large number of studies have demonstrated that miRNA has an effect on the development of OS by targeting the Wnt signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑1236‑3p inhibits human osteosarcoma growth

Chen

et al. 2020

Oncol Lett

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Osteosarcoma (OS) is a common bone tumor with high mortality worldwide. The long-term survival rate of patients with metastatic or recurrent disease is <20%. The present study explored the biological role of microRNA (miRNA/miR)-1236-3p in OS. miRNA and mRNA expression levels were measured via reverse transcription-quantitative PCR. Fluorescence in situ hybridization was performed to determine miR-1236-3p expression levels in clinical specimens. Protein expression was measured via western blotting. Immunohistochemical analysis was used to detect Wnt target gene expression in tumor tissues. The interaction between the Wnt3a 3′untranslated region and miR-1236-3p was assessed via dual-luciferase reporter assays. Cell cycle, Transwell, Cell Counting Kit-8 and wound healing assays were conducted to evaluate the function of the miR-1236-3p/Wnt3a axis. Human OS (HOS) cells stably transfected with vector or miR-1236-3p sponge were injected subcutaneously into nude mice to assess the role of miR-1236-3p in vivo . miR-1236-3p expression was downregulated in OS tissues compared with chondroma tissues, and miR-1236-3p overexpression inhibited OS cell migration and proliferation compared with the negative control group. Furthermore, in vivo xenograft assays displayed enhanced tumour growth rates in the miR-1236-3p sponge group compared with the vector control group. In the present study, the results indicated that miR-1236-3p inhibited OS progression and Wnt3a was identified as a target of miR-1236-3p.

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Section: Discussionmentioning

confidence: 99%

MicroRNA‑1236‑3p inhibits human osteosarcoma growth

Chen

et al. 2020

Oncol Lett

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“…β-Catenin is a multifunctional protein, which exists in cells in two forms: (1) binding type, in which β-catenin binds to the inner surface of cell membrane with E-cadherin to form Ecadherin/catenin complex, which mediates the adhesion between homologous cells; (2) free type, in which β-catenin participates in the Wnt signal transduction pathway, enters the nucleus through nuclear membrane, binds to LEF/TCF, and activates Wnt pathway target genes, such as c-Myc, cyclin D1, MMP-7, and CD44; all those genes play an important role in the development of tumors (27)(28)(29). Numerous of studies have also shown that high expression of β-catenin is associated with lung metastasis and poor prognosis in patients with osteosarcoma and shows poor prognosis (18,19,30). Furthermore, inhibition of βcatenin expression can inhibit the growth and lung metastasis of osteosarcoma xenografts in nude mice (31)(32)(33).…”

Section: Discussionmentioning

confidence: 99%

Prognostic Significance of β-Catenin Expression in Osteosarcoma: A Meta-Analysis

Xie

Zhu

et al. 2020

Front. Oncol.

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Background: β-catenin plays a crucial role in the progression of osteosarcoma. However, the clinical significance of β-catenin over-expression in osteosarcoma still remains unclear. Thus, we performed a meta-analysis of studies that evaluated the impact of β-catenin on metastasis and overall survival (OS) in osteosarcoma.Methods: We searched PubMed, The Cochrane Library, Embase, Springer, Science Direct, OVID, Weipu, Wanfang and China National Knowledge Internet (CNKI) databases from their start year up to Aug.2019. Individual hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted and pooled HRs with 95% CIs or odd ratio (OR) were used to evaluate the relationships between β-catenin over-expression and metastasis and overall survival in osteosarcoma.Results: Eight related studies involving 521 patients were qualified for this meta-analysis. Results showed that over-expression of β-catenin was significantly correlated with metastasis (OR = 3.31, 95% CI = 2.08-5.24, P < 0.001) and overall survival (HR = 2.32, 95% CI = 1.48-363, P = 0.02). Conclusion:The meta-analysis revealed that over-expression of β-catenin might be associated with distant metastasis and overall survival in osteosarcoma, which reminds that β-catenin acts as a prognostic biomarker and it can guide the clinical therapy in osteosarcoma patients.

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“…The canonical Wnt/β-catenin pathway, which plays a crucial role in osteoblast differentiation, has been found to lead to osteoblast proliferation and suppression of osteogenic differentiation in adult mesenchymal cells through expression of Wnt3a [51][52][53][54]. Moreover, aberrations of Wnt signaling pathway have been associated with osteosarcoma tumorigenesis and osteosarcoma drug resistance through upregulation of factors, such as c-Met, leading to stem-cell phenotypes [4,[55][56][57][58]. LncRNA H19 has been found to increase Wnt signaling through epigenetical regulation of the Wnt pathway antagonist NKD1 via EZH2 recruitment [59].…”

Section: Lncrnas and Signal Transduction Pathways 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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The canonical Wnt-beta-catenin pathway in development and chemotherapy of osteosarcoma

Cited by 27 publications

References 54 publications

MicroRNA‑1236‑3p inhibits human osteosarcoma growth

MicroRNA‑1236‑3p inhibits human osteosarcoma growth

Prognostic Significance of β-Catenin Expression in Osteosarcoma: A Meta-Analysis

Long Noncoding RNAs in Osteosarcoma: Mechanisms and Potential Clinical Implications

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