GATA3 is downregulated in osteosarcoma and facilitates EMT as well as migration through regulation of slug

Ma, Linjie; Xue, Wei; Ma, Xianghai

doi:10.2147/ott.s176534

Cited by 16 publications

(18 citation statements)

References 35 publications

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“…EMT serves key roles in cancer metastasis ( 27 ). In corroboration with previous studies ( 17 , 28 ), the present study demonstrated that GATA3 suppressed EMT in HCC cells by increasing the expression of E-cadherin and decreasing the expression of N-cadherin and vimentin. In addition, qChIP and dual luciferase reporter assays demonstrated that GATA3 transcriptionally regulated slug, thereby inhibiting EMT in HCC.…”

Section: Discussionsupporting

confidence: 93%

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GATA3 is downregulated in HCC and accelerates HCC aggressiveness by transcriptionally inhibiting slug expression

et al. 2021

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Previous studies have reported that GATA3 is downregulated in multiple types of tumours, including gastric cancer and osteosarcoma. The aim of this study was to explore whether GATA3 serves as a tumour suppressor to inhibit hepatocellular carcinoma (HCC) development. Tumour tissue specimens and adjacent normal tissue specimens were obtained from 162 patients diagnosed with HCC in the Affiliated Hospital of Shaoxing University from July 2000 to May 2018. The result of the present study demonstrated that GATA3 was downregulated in HCC tumour tissues compared with that of adjacent normal tissues. The expression of GATA3 was also negatively associated with tumour size, TNM stage and lymph node metastasis. Additionally, analysis of the follow-up data revealed that low GATA3 expression was closely correlated with poor survival. Gain and loss of function analyses revealed that overexpression of GATA3 decreased the ability of proliferation, migration and invasion in HCC cell lines, whereas inhibition of GATA3 promoted the ability of proliferation, migration and invasion. In addition, GATA3 suppressed EMT through the regulation of slug expression. Additionally, slug overexpression attenuated the inhibitory effects of GATA3 overexpression on cancer cell proliferation, migration and invasion. Thus, GATA3 is downregulated in HCC, and suppresses cell proliferation, migration and invasion. Moreover, GATA3 transcriptionally inhibits slug expression, thereby suppressing EMT in HCC.

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Section: Discussionsupporting

confidence: 93%

“…4A and C ). Notably, a previous study demonstrated that GATA3 regulates the expression of slug in osteosarcoma ( 17 ). Thus, whether GATA3 regulated slug expression in HCC was determined.…”

Section: Resultsmentioning

confidence: 99%

GATA3 is downregulated in HCC and accelerates HCC aggressiveness by transcriptionally inhibiting slug expression

et al. 2021

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“…A reciprocal feedback regulatory loop between GATA3 / G9A / MTA3 and ZEB2 / G9A / MTA1 has recently been identified; the absence of GATA3 in this axis contributes to breast cancer invasion and metastasis by upregulating the ZEB2 expression levels ( 65 ). GATA3 has also been reported to suppress osteosarcoma EMT progression by targeting the transcription factor Slug ( 66 ). The present study demonstrated for the first time that GATA3 was involved in the immunomodulation of osteosarcoma.…”

Section: Discussionmentioning

confidence: 99%

Identification of prognostic biomarkers associated with metastasis and immune infiltration in osteosarcoma

Yang

Chen

et al. 2021

Oncol Lett

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Osteosarcoma is the most common primary malignancy of the bones, and is associated with a high rate of metastasis and a poor prognosis. A tight association between the tumor microenvironment (TME) and osteosarcoma metastasis has been established. In the present study, the Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) algorithm was applied to calculate the immune and stromal scores of patients with osteosarcoma based on data from The Cancer Genome Atlas database. A metagene approach and deconvolution method were used to reveal distinct TME landscapes in patients with osteosarcoma. Bioinformatics analysis was used to identify differentially expressed genes (DEGs) associated with metastasis and immune infiltration in osteosarcoma, and a risk model was constructed using the DEGs with potential prognostic significance. Subsequently, gene set enrichment and Spearman's correlation analyses were used to delineate the biological processes associated with these prognostic biomarkers. Finally, immunohistochemical (IHC) analysis was performed to evaluate the expression levels of immune infiltrates and prognostic biomarkers in clinical osteosarcoma tissues. The results of the ESTIMATE demonstrated that patients with non-metastatic osteosarcoma presented with higher immune/stromal scores and a more favorable prognosis compared with those with metastatic osteosarcoma. The TME landscapes in patients with osteosarcoma suggested that high levels of tumor-infiltrating immune cells (TIICs) may suppress metastasis. Increased numbers of CD56 bright natural killer cells, immature B cells, M1 macrophages and neutrophils, and lower levels of M2 macrophages were observed in the non-metastatic tissues compared with those in the metastatic tissues. A total of 69 DEGs were identified to be associated with metastasis and immune infiltration in osteosarcoma. Of these, GATA3, LPAR5, EVI2B, RIAM and CFH exhibited prognostic potential and were highly expressed in non-metastatic osteosarcoma tissues based on the IHC analysis results. These biomarkers were involved in various immune-related biological processes and were positively associated with multiple TIICs and immune signatures. The risk model constructed using these prognostic biomarkers demonstrated high predictive accuracy for the prognosis of osteosarcoma. In conclusion, the present study proposed a five-biomarker prognostic signature for the prediction of metastasis and immune infiltration in patients with osteosarcoma.

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“…Inactivation of the Wnt/beta-catenin signaling inhibits angiogenesis and induces cell apoptosis in osteosarcoma cells by inducing autophagy [ 38 ]. Inhibition of EMT serves as a tumor suppressor in osteosarcoma by suppressing the progression and metastasis [ 39 ]. Furthermore, EMT inactivation inhibited proliferation, migration, invasion, and in osteosarcoma by targeting zinc finger E-box-binding protein 1 (ZEB1) through inactivation of c-Jun N-terminal kinase (JNK) and JAK1/signal transducer and activator of transcription 3 (STAT3) pathways [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

“…Studies have found that the Wnt/β-catenin and EMT signaling pathways are associated with tumor cell proliferation, apoptosis, and cell cycle regulation [37][38][39]. Aberrant activation of Wnt signaling has been implicated in human osteosarcoma, and Wnt/β-catenin signaling plays the critical role in human osteosarcoma pathogenesis and growth [37].…”

Section: Discussionmentioning

confidence: 99%

miRNA-128 modulates bone neoplasms cells proliferation and migration through the WNT/β-catenin and EMT signal pathways

Long

Wang

et al. 2021

J Orthop Surg Res

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Background Bone neoplasms present poor prognosis due to recurrence and metastasis. Although the role microRNAs (miRNAs) in inhibiting growth and metastasis of bone neoplasms has been investigated, the underlying potential molecular mechanisms mediated by miRNA-128 (miR-218) for the invasiveness of bone neoplasms cells are still not completely understood. The purpose of this study was to identify the regulatory mechanisms of miR-218 in bone neoplasms cells. Methods Western blotting, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Counting Kit-8 assay, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, luciferase activity assay immunofluorescence, and immunohistochemistry were used to analyze the regulatory effects of miR-218 on bone neoplasms cells. Results Here, the results showed that transfection of miR-128 suppressed bone neoplasms cells proliferation, migration, and invasion. Genetic knockdown of miR-128 in bone neoplasms cells suppressed the activation of the Wnt/β-catenin and epithelial-mesenchymal transition (EMT) signaling pathways. Activation of Wnt or EMT blocked miR-128-inhibited cells proliferation and migration in bone neoplasms cells. Exogenously introduced miR-128 markedly inhibited tumor regeneration in bone neoplasms xenograft models. Conclusions These results define a tumor-regulated function for miR-128 in bone neoplasms by down-regulation of the Wnt/β-catenin and EMT signal pathways, which provided a potential target for bone neoplasms gene therapy.

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GATA3 is downregulated in osteosarcoma and facilitates EMT as well as migration through regulation of slug

Cited by 16 publications

References 35 publications

GATA3 is downregulated in HCC and accelerates HCC aggressiveness by transcriptionally inhibiting slug expression

GATA3 is downregulated in HCC and accelerates HCC aggressiveness by transcriptionally inhibiting slug expression

Identification of prognostic biomarkers associated with metastasis and immune infiltration in osteosarcoma

miRNA-128 modulates bone neoplasms cells proliferation and migration through the WNT/β-catenin and EMT signal pathways

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