Promoter hypermethylation of the cysteine protease RECK may cause metastasis of osteosarcoma

Wang, Leisheng; Ge, Jian; Ma, Tian; Zheng, Yanpin; Lv, Shiqiao; Li, Yu; Liu, Shaoxian

doi:10.1007/s13277-015-3688-4

Cited by 11 publications

(11 citation statements)

References 15 publications

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“…RECK is usually reported as a tumor suppressor, particularly an inhibitor of metastasis, in many types of cancer. 14 , 15 , 27 In this study, the suppressive effect of RECK on GC cells was confirmed, and RECK was inhibited by miR-590-5p. Additionally, other miRNAs, including miR-221, miR-222, miR-374-5p, and miR-25, also regulated RECK by binding to its 3′-UTR and contributing to the growth and invasion of GC.…”

Section: Discussionsupporting

confidence: 65%

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miR-590-5p regulates gastric cancer cell growth and chemosensitivity through RECK and the AKT/ERK pathway

Shen¹,

Yu²,

Zhang³

et al. 2016

OTT

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BackgroundThe aim of this study was to determine the role of miRNA-590-5p in gastric cancer (GC) progression.MethodsQuantitative real-time polymerase chain reaction was performed to measure endogenous miR-590-5p levels in GC cells and tissues. Overexpression or knockdown of miR-590-5p in GC cells was performed by transfection with mimics or an inhibitor, respectively. MTT, matrigel transwell, and Western blot assays were used to assess the effects of miR-590-5p on cell proliferation, invasion, chemosensitivity of GC cells, and the AKT pathway, respectively. In silico prediction and luciferase reporter activity were used to identify potential targets of miR-590-5p. A xenograft model was also established to evaluate the function of miR-590-5p in vivo.ResultsThe expression of miR-590-5p was significantly increased in GC cells and tissues, and upregulated miR-590-5p was associated with increased tumor size, lymph node metastasis, and poor survival. Overexpression of miR-590-5p promoted cell proliferation and invasion and reduced the sensitivity of GC cells to cisplatin and paclitaxel. In contrast, inhibition of miR-590-5p had the opposite effects on GC cells. RECK was identified as a direct target of miR-590-5p. Knockdown of RECK accelerated cell proliferation and motility and decreased the drug sensitivity. Furthermore, reintroduction of RECK inhibited the oncogenic effects of miR-590-5p by suppressing cell proliferation and invasion and increasing drug sensitivity. We found that the AKT/ERK and STAT3 signaling pathways were activated by miR-590-5p overexpression. The chemoresistance of miR-590-5p was also verified by in vivo analysis.ConclusionIn summary, we suggest that the miR-590-5p/RECK/AKT axis contributes to GC and may serve as a promising therapeutic target for treatment.

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Section: Discussionsupporting

confidence: 65%

“… 12 Loss of RECK is correlated with metastasis in lung cancer, hepatoblastoma, and osteosarcoma. 13 – 15 RECK inhibited tumorigenicity of GC by suppressing NOTCH1 signaling. 16 Hypoxia- and RAS-signaling cooperatively downregulated the expression of RECK, thereby promoting malignant cell behavior.…”

Section: Introductionmentioning

confidence: 99%

miR-590-5p regulates gastric cancer cell growth and chemosensitivity through RECK and the AKT/ERK pathway

Shen¹,

Yu²,

Zhang³

et al. 2016

OTT

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“…These genes were hypermethylated in various types of tumors and were involved in tumor-associated biological processes. For example, promoter methylation of RECK contributes to metastasis of osteosarcoma (9). BRCA1 negatively mediates cell proliferation, and its mRNA levels were downregulated by methylation (10).…”

Section: Introductionmentioning

confidence: 99%

Epigenetically silenced PTPRO functions as a prognostic marker and tumor suppressor in human lung squamous cell carcinoma

Ming

Sun

2017

Molecular Medicine Reports

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Protein tyrosine phosphatase receptor-type O (PTPRO), a member of the PTP family, has been frequently reported as potential tumor suppressor in many types of cancer. However, the exact function of PTPRO in lung squamous cell carcinoma (LSCC) remains unclear. Bisulfite sequencing and methylation specific polymerase chain reaction (PCR) were used to identify the methylation status of PTPRO in LSCC cells, and quantitative methylation specific PCR was used to evaluate the methylation levels of PTPRO in LSCC patients. Stably expressing PTPRO vectors were constructed and transfected into H520 and SK-MES-1 cells, followed by MTT and colony formation assays, and analysis of tumor weight and volume in in vivo mouse xenograft models. The present study demonstrated that the CpG island of PTPRO exon 1 was obviously hypermethylated in LSCC cells and tissues. The mRNA expression of PTPRO could be restored by treatment with a demethylation agent. Increased methylation and decreased mRNA levels of PTPRO were observed in LSCC samples compared with adjacent healthy tissues, and were associated with poor prognosis of patients. The mRNA expression of PTPRO was negatively correlated with its methylation level in tumors. Functionally, ectopic PTPRO expression in LSCC cells significantly inhibited the proliferation rates, and colony formation, in comparison with control and non-transfected cells. In vivo assays confirmed the inhibitory effect of PTPRO on LSCC cell growth. In conclusion, these data provided evidence that epigenetic regulation of PTPRO impairs its tumor suppressor role in LSCC, and restoration of PTPRO may be a potential therapeutic strategy.

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“…DNA hypermethylation in promoter is a key characteristic in cancer and it was considered to be able to silence the tumor suppressor genes to induce the development of cancer (14)(15)(16). Some DNA methylation was also observed in OS and found to be associated with its progression, the methylation level of RECK was gradually increased with the development of OS, while the opposite trend of its expres-sion profile was observed (17). In the study of Sonaglio et al, the differential ESR1 and p14ARF gene methylation profiles were also identified as prognostic indicators in OS (18).…”

Section: Introductionmentioning

confidence: 99%

Combined analysis of gene expression, miRNA expression and DNA methylation profiles of osteosarcoma

2016

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Osteosarcoma (OS) is a common primary malignancy in children and adolescents with relative high survival rate after chemotherapy. While the toxicity of chemotherapy and personalized different response to chemotherapy makes it difficult for the selection of therapeutics and improvement of diagnosis. In this study, we conducted a combined analysis of three types of microarray datasets (gene expression, microRNA (miRNA) expression and DNA methylation) from the Gene Expression Omnibus (GEO). The differential expression genes (DEGs) and miRNAs (DEMI) were screened out via the limma package and differential methylation sites (DMS) were identified by the IMA package. Enriched functions of DEGs and genes contained DMS (DEMs) were obtained through the Database for Annotation, Visualization and Integrated Discovery (DAVID). Besides, miRNA-gene regulation network was obtained based on the pairs of involved DEMIs and overlapping genes between DEMs and DEGs and visualized through Cytoscape software. A total of 583 DEGs and 1051 DMS (corresponding to 827 DEMs) were identified and 56 overlaps were obtained. As expected, most of the expression and methylation profiles of the overlaps exhibited significant negative correlation. The DEGs were mainly enriched in the biological processes related to inflammatory/immune response, cell proliferation, while DEMs were involved in the regulation of gene expression, tissue/organ development. Based on the correlation and network analysis, some novel targets were identified for OS and many known biomarkers were proved in this study, which would be helpful in its early diagnosis and treatment.

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Promoter hypermethylation of the cysteine protease RECK may cause metastasis of osteosarcoma

Cited by 11 publications

References 15 publications

miR-590-5p regulates gastric cancer cell growth and chemosensitivity through RECK and the AKT/ERK pathway

miR-590-5p regulates gastric cancer cell growth and chemosensitivity through RECK and the AKT/ERK pathway

Epigenetically silenced PTPRO functions as a prognostic marker and tumor suppressor in human lung squamous cell carcinoma

Combined analysis of gene expression, miRNA expression and DNA methylation profiles of osteosarcoma

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