Low expression of GATA3 promotes cell proliferation and metastasis in gastric cancer

Wei, Shuangqin; Liu, Zhong; Wang, Xiaoping; Zhang, Wenju

doi:10.2147/cmar.s147973

Cited by 10 publications

(10 citation statements)

References 31 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%

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%

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

et al. 2021

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“…Our results revealed that GATA4 methylation was related to the clinical stage, lymph node metastasis and tumor differentiation. Interestingly, a research mainly published by Shuangqin Wei showed that the expression of GATA3 was associated with tumor size, stage and metastasis in GC, but there were no correlations between the expression of GATA3 and gender, age, pathological grade of cancer and alcohol consumption of patients [15], which was highly in line with our findings. Our work strongly demonstrated that GATA4 played a significant role in GC development and GATA4 methylation may be a potential marker for early diagnosis of GC.…”

Section: Discussionsupporting

confidence: 89%

“…It is generally recognized that GC is one of the most prevalent malignant tumors in alimentary canal and is seen as a major health problem due to its high frequency, aggressiveness and low cur e rate [14]. A recent report revealed that GATA3 could serve as an oncogene in GC development and potentially act as a novel therapeutic target [15]. But there were few researches about the mechanism of GATA4 in GC development.…”

Section: Discussionmentioning

confidence: 99%

“…GATA4 silencing reduced the proliferation of YCC3 cells, one kind of GC cells[10]. Restoration of GATA3 suppressed GC cell proliferation, migration and invasion[15]. Besides, GATA4 overexpression hadreported to repress colony formation, proliferation, migration and invasion abilities of colorectal cancer cell, thus exerting tumor suppressive effects in colorectal cancer cells in vitro [20] more, restoration of GATA4 expression was also found to inhibit proliferation and colony formation ability, as well as induce apoptosis of hepatocellular carcinoma cells [21].…”

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confidence: 97%

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Effect of GATA4 gene methylation on proliferation and apoptosis of SGC-7901 gastric cancer cells

Ma¹,

Ji²

2021

neo

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Gastric cancer (GC) remains a major cause of cancer-related deaths worldwide. GATA4 has been previously reported to exhibit functions in GC. In this study, we aimed to investigate effect of GATA4 gene methylation on GC progression. Methylation-Sensitive High-Resolution Melting was used to detect the methylation of GATA4 promoter region in GC tissues and adjacent normal tissues, GC cell lines and GES-1 cells. The relationship between GATA4 methylation level and clinical characteristics of GC patients was analyzed. GATA4 levels in GC tissues and adjacent normal tissues, GC cell lines and GES-1 cell lines were detected, and gain-of function was performed to investigate the role of GATA4 in GC. Si-GATA4 was transfected into GES-1 cells to observe the changes of various indicators. RNA-seq detected the differentially expressed genes in SGC-7901 cells overexpressing GATA4, and western blot analysis verified their expression. GATA4 methylation rate was increased in GC tissues, and GATA4 promoter was abnormally methylated in GC cells. GATA4 methylation rate in GC tissues was related to lymph node metastasis, differentiation degree and clinical stage of GC patients. Lower expressed GATA4 was observed in GC tissues and cells. Cell proliferation rate decreased and cell apoptosis rate increased in SGC-7901 cells overexpressing GATA4. Transfecting si-GATA4 into GES-1 cells led to increased proliferation, inhibited apoptosis, and restoration of GATA4 led to decreased APC an levels. In conclusion, restoration of GATA4 caused by 5-Aza treatment can inhibit the proliferation-catenin signaling pathway. This study may offer new sight for GC treatment.

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“…A reverse correlation was confirmed between GATA3 and FMNL1 expressions in clinical samples. Gene silencing of GATA3 was documented in several cancers (18)(19)(20) and re-expression of GATA3 was capable of inhibiting tumor metastasis (21)(22)(23). However, the precise mechanism of FMNL1 regulation by GATA3 was not clear and requires further investigation.…”

Section: Discussionmentioning

confidence: 99%

FMNL1 Exhibits Pro-Metastatic Activity via CXCR2 in Clear Cell Renal Cell Carcinoma

Zhang

Yang

et al. 2020

Front. Oncol.

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Formin-like (FMNL) proteins are responsible for cytoskeletal remodeling and have been implicated in the progression and spread of human cancers. Yet the clinical significance and biological function of FMNL1 in clear cell renal cell carcinoma (ccRCC) remain unclear. In this study, the expression of FMNL1 in ccRCC and its clinical value were determined by tissue microarray-based IHC and statistical analyses. The role of FMNL1 in ccRCC metastasis and the underlying mechanism were investigated via in vitro and in vivo models using gene regulation detection, ChIP, Luciferase reporter assays, and rescue experiments. We show that FMNL1 is upregulated in ccRCC and exhibits pro-metastatic activity via induction of CXCR2. High expression of FMNL1 is significantly correlated with advanced tumor stage, higher pathological tumor grade, tumor metastasis, and unfavorable prognosis in two independent cohorts containing over 800 patients with ccRCC. The upregulation of FMNL1 in ccRCC is mediated by the loss of GATA3. Ectopic expression of FMNL1 promotes, whereas FMNL1 depletion inhibits cell migration in vitro and tumor metastasis in vivo. The FMNL1-enhanced cell mobility is markedly attenuated by the knockdown of CXCR2. Further studies demonstrate that FMNL1 increases the expression of CXCR2 via HDAC1. In clinical samples, FMNL1 expression is positively associated with CXCR2, and is negatively connected to GATA3 expression. Collectively, our data suggest FMNL1 serve as a potential prognostic factor and function as an oncogene. The axis of GATA3/FMNL1/CXCR2 may present a promising therapeutic target for tumor metastasis in ccRCC.

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Low expression of GATA3 promotes cell proliferation and metastasis in gastric cancer

Cited by 10 publications

References 31 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

Effect of GATA4 gene methylation on proliferation and apoptosis of SGC-7901 gastric cancer cells

FMNL1 Exhibits Pro-Metastatic Activity via CXCR2 in Clear Cell Renal Cell Carcinoma

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