Biomarkers for gastric cancer: Progression in early diagnosis and prognosis (Review)

Jin, Ziliang; Jiang, Weihua; Wang, Liwei

doi:10.3892/ol.2015.2959

Cited by 85 publications

(64 citation statements)

References 102 publications

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“…Because of a lack of understanding regarding the pathogenesis of GC and the lack of a specific targeted gene therapy, chemotherapy, and surgical techniques do not satisfactorily enhance the survival rate of patients with GC . Some studies have indicated that genetic alteration may play a crucial role in the development of GC and carcinogenesis . Several genetic alterations which can be used as prognostic biomarkers include oncoproteins such as protein kinase CK2, VAV3, and SOX4, as found in our laboratory, and tumor suppressors such as miR‐429 and miR‐1225‐5p, as found in other laboratories .…”

Section: Introductionmentioning

confidence: 57%

Ceramide synthase 6 predicts the prognosis of human gastric cancer: It functions as an oncoprotein by dysregulating the SOCS2/JAK2/STAT3 pathway

Uen

Fang

Lin

et al. 2018

Molecular Carcinogenesis

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Although gastric cancer (GC) is one of the most common cancers, knowledge of its development, and carcinogenesis is limited. The present study explored the involvement of ceramide synthase 6 (CERS6) in GC carcinogenesis and prognosis. RT-PCR, immunoblotting, and immunohistochemistry were used to examine the expression of CERS6. Transfection and small hairpin RNA technology were used to investigate the effect of CERS6 manipulation on cell proliferation and spread as well as the underlying mechanism. Moreover, xenograft proliferation was employed to explore the influence of CERS6 on tumor growth in animals. It was found that overexpression of CERS6 was significantly correlated with several clinicopathologic parameters and poor disease-free survival. The overexpression and silencing of CERS6 in GC cells facilitated and suppressed cell proliferation and spread as well as xenograft proliferation, respectively. Mechanistic studies further revealed that CERS6 influenced cell proliferation and spread by regulating cell cycle control and metastasis-related protein through the SOCS2/JAK2/STAT3 signaling pathway. Collectively, this study suggests that CERS6 overexpression could be a useful biomarker for predicting the outcomes of GC patients and that CERS6 targeting represents a potential modality for treating GC.

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Section: Introductionmentioning

confidence: 57%

Ceramide synthase 6 predicts the prognosis of human gastric cancer: It functions as an oncoprotein by dysregulating the SOCS2/JAK2/STAT3 pathway

Uen

Fang

Lin

et al. 2018

Molecular Carcinogenesis

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“…Studies show that dysfunction of intrinsic miRNA regulatory mechanisms results in abnormal expression of various oncogenes and tumor suppressor genes in a variety of tumor types (18); therefore, miRNAs may act as both oncogenes and tumor suppressor genes. miRNAs have been implicated in the biology of gastric cancer (19,20): miRNA array analysis has shown that expression of miR-21, miR-191, miR-223, miR-24, miR-107, miR-92 and miR-221 is elevated in gastric cancer (21), while that of miR-128b, miR-129 and miR-148 is decreased (22). Gastric cancer is a disease involving the complex activation and inactivation of multiple genes; miRNAs may therefore assume the role of both oncogene and tumor suppressor in the onset and development of this disease.…”

Section: Discussionmentioning

confidence: 99%

miRNA-223 inhibits epithelial-mesenchymal transition in gastric carcinoma cells via Sp1

Shan

Hu³

et al. 2016

International Journal of Oncology

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Abstract. Sp1 plays critical roles in epithelial-mesenchymal transition (EMT) of certain cancer. However, few studies have indicated whether Sp1 is involved in the EMT of gastric cancer, and whether abnormal expression of Sp1 in gastric cancer EMT is regulated in a post-transcriptional manner, and the involvement of miRNAs in this regulation. In this study, we selected 20 cases of gastric cancers, their liver metastases and para-carcinoma tissues to examine the levels of Sp1 protein and mRNA by immunohistochemistry and fluorescent PCR, which showed that Sp1 was increased in gastric cancers and their metastases compared with adjacent tissues, but there was no difference in Sp1 mRNA between these three groups, suggesting changes in Sp1 may be attributed to inactivation of post-transcriptional regulation. We verified by a luciferase reporter system that miRNA-223 binds to 3'-UTR of Sp1 gene and inhibits its translation, in agreement with negative correlation between miRNA-223 and Sp1 protein levels in gastric cancer cells. By employing TGF-β1 to induce MGC-803, BGC-823 and SGC-7901, we successfully built cellular EMT model. Then, we overexpressed miRNA-223 in the model by using a lentiviral system, which diminished EMT indicators and suppressed proliferation and invasion ability, and induced apoptosis. Finally, we verified the specificity of the regulation pathway miRNA-223/Sp1/EMT. These findings suggest that low expression of miRNA-223 in gastric cancer cells is an important cause for EMT. miRNA-223 specifically regulates the EMT process of gastric cancer cells through its target gene Sp1. Overexpression of miRNA-223 in these cells inhibits EMT via the miRNA-223/Sp1/EMT pathway.

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“…DNA methylation is the most common epigenetic modification, and is involved in various biological processes, including tumorigenesis, when aberrant DNA methylation occurring in promoter CpG islands can lead to gain of function in oncogenes and loss of function in tumor suppressor genes (1)(2)(3)(4). The mechanism by which DNA hypomethylation contributes to tumorigenesis has been proposed to involve chromosomal instability (5,6), derepression of imprinted genes (7), and retrotransposon activation (8,9).…”

Section: Introductionmentioning

confidence: 99%

LINE-1 hypomethylation is inversely correlated with UHRF1 overexpression in gastric cancer

et al. 2018

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DNA methylation is an important epigenetic modification that alters gene expression; DNA hypomethylation contributes to tumorigenesis through multiple processes. In the present study, the methylation of long interspersed element-1 (LINE-1) in 95 gastric cancer (GC) tissues and matched adjacent normal tissues was investigated by pyrosequencing. LINE-1 methylation was compared with the expression of ubiquitin-like with PHD and ring-finger protein 1 (UHRF1), an essential regulator of DNA methylation, using reverse transcription-quantitative polymerase chain reaction. Significant hypomethylation of LINE-1 and overexpression of UHRF1 were observed in GC tissues compared with the matched controls (P<0.001 and P=0.001, respectively). LINE-1 hypomethylation was inversely correlated with UHRF1 overexpression in GC tissues (r=-0.026, P=0.028). In addition, LINE-1 hypomethylation in GC was significantly associated with Lauren's histological classification, tumor differentiation and background intestinal metaplasia (P=0.014, P=0.042 and P=0.034, respectively). These results suggest that LINE-1 hypomethylation may be a potential biomarker for GC and it is indirectly regulated by UHRF1 overexpression.

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Biomarkers for gastric cancer: Progression in early diagnosis and prognosis (Review)

Cited by 85 publications

References 102 publications

Ceramide synthase 6 predicts the prognosis of human gastric cancer: It functions as an oncoprotein by dysregulating the SOCS2/JAK2/STAT3 pathway

Ceramide synthase 6 predicts the prognosis of human gastric cancer: It functions as an oncoprotein by dysregulating the SOCS2/JAK2/STAT3 pathway

miRNA-223 inhibits epithelial-mesenchymal transition in gastric carcinoma cells via Sp1

LINE-1 hypomethylation is inversely correlated with UHRF1 overexpression in gastric cancer

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