Knockdown of FRAT1 inhibits hypoxia-induced epithelial-to-mesenchymal transition via suppression of the Wnt/β-catenin pathway in hepatocellular carcinoma cells

Fan, Wanhu; Du, Fenjing; Liu, Xiaojing; Chen, Na

doi:10.3892/or.2016.5130

Cited by 15 publications

(10 citation statements)

References 27 publications

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“…For example, Fan et al . reported that FRAT1 knockdown hindered hypoxia‐induced cell migration and invasion through suppression of the Wnt/β‐catenin pathway in hepatocellular carcinoma . However, the role of FRAT1 and the regulatory network of SNHG1/miR‐361‐3p/FRAT1 axis need to be confirmed.…”

Section: Introductionmentioning

confidence: 98%

LncRNA SNHG1 influences cell proliferation, migration, invasion, and apoptosis of non‐small cell lung cancer cells via the miR‐361‐3p/FRAT1 axis

Zheng

2019

Thoracic Cancer

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Background: Non-small-cell lung cancer (NSCLC) is the most lethal type of cancer. Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) have been identified as crucial regulators in the development of NSCLC. The aim of our study was to explore the molecular mechanism of SNHG1 to enable better treatment for NSCLC patients. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the expression of Small nucleolar RNA host gene 1 (SNHG1), miR-361-3p and frequently rearranged in advanced T-cell lymphomas 1 (FRAT1). The protein level of FRAT1 was measured by western blot assay. Cell proliferation was evaluated by methyl thiazolyl tetrazolium (MTT) assay. Cell apoptosis was assessed by flow cytometry assay. The number of migrated and invaded cells were counted by transwell assay. The relationship between miR-361-3p and SNHG1 or FRAT1 was confirmed by dual-luciferase reporter assay. Results: Our results indicated that SNHG1 and FRAT1 were highly expressed in NSCLC tissues and cells. SNHG1 silencing inhibited proliferation, induced apoptosis and blocked migration and invasion of NSCLC cells. Also, FRAT1 downregulation suppressed proliferation, promoted apoptosis and hindered migration and invasion of NSCLC cells. Further, FRAT1 could recover the effects of SNHG1 silencing on proliferation, apoptosis, migration and invasion of NSCLC cells. SNHG1 sponged miR-361-3p and negatively regulated miR-361-3p expression. Meanwhile, miR-361-3p targeted FRAT1 and inversely modulated FRAT1 expression. In addition, miR-361-3p inhibition abated the effect of SNHG1 knockdown on FRAT1 expression. Conclusion: In conclusion, LncRNA SNHG1 promoted the proliferation, repressed apoptosis and enhanced migration and invasion of NSCLC cells by regulating FRAT1 expression via sponging miR-361-3p.

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Section: Introductionmentioning

confidence: 98%

LncRNA SNHG1 influences cell proliferation, migration, invasion, and apoptosis of non‐small cell lung cancer cells via the miR‐361‐3p/FRAT1 axis

Zheng

2019

Thoracic Cancer

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“…For this assay, 100 µl Matrigel (BD Biosciences, San Jose, CA, USA) was coated onto the upper chamber. The infected cells (5x10 4 ) were seeded in the upper chamber of the wells in 100 µl FBS-free medium, while the lower chambers were filled with 600 µl 20% FBS medium. Following incubation for 24 h, the top layer of the insert was scrubbed with a sterile cotton swab to remove any remaining cells.…”

Section: Small Interferingmentioning

confidence: 99%

“…Epithelial-mesenchymal transition (EMT) is an important mechanism leading to invasion and metastasis of various cancers (4)(5)(6). Cells undergoing EMT lose the epithelial features and acquire some mesenchymal features, which is associated with the upregulation of N-cadherin and downregulation of E-cadherin (6).…”

Section: Introductionmentioning

confidence: 99%

Long non-coding RNA CCAT2 promotes epithelial-mesenchymal transition involving Wnt/β-catenin pathway in epithelial ovarian carcinoma cells

et al. 2017

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Abstract. Long non-coding RNA colon cancer-associated transcript 2 (CCAT2) is dysregulated in a variety of types of human cancer. However, the role of CCAT2 in epithelial ovarian carcinoma (EOC) remains largely unknown. The aim of this study is to investigate the effect of CCAT2 on epithelial-mesenchymal transition (EMT) and related molecular mechanisms in epithelial ovarian cancer cells. In the current paper, we found that CCAT2 was significantly upregulated in EOC SKOV3, A2780 and HO8910 cell lines compared with the normal ovarian epithelial HUM-CELL-0088 cell line. Functional assays demonstrated that the knockdown of CCAT2 inhibited migration and invasion of EOC cells in vitro. Moreover, our results showed that silencing CCAT2 inhibited EMT by the upregulation of epithelial cadherin and downregulation of neural cadherin, zinc finger protein SNAI and Twist-related protein 1 in SKOV3 and A2780 cell lines. But, that was reversed by the treatment with lithium chloride (LiCl), by which the canonical Wnt/β-catenin pathway could be activated. In addition, we further investigated the role of CCAT2 in the modulation of Wnt/β-catenin signaling pathway. Our results revealed that knockdown of CCAT2 inhibited the expression of β-catenin and the activity of T-cell factor/lymphoid enhancer factor, acting as a key transcription factor of Wnt signaling pathway. Collectively, these results indicate that CCAT2 may promote EMT, at least partly through Wnt/β-catenin signaling pathway in EOC cells. Thus, CCAT2 might play a critical role in EOC progression and serve as a valuable target for the treatment of ovarian cancer.

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“…FRAT1 protein has a molecular weight of 29 kD, containing 279 amino acids. As an extensively recognized oncogene, FRAT1 is overexpressed in ovarian cancer [42], non-small cell lung cancer [43], pancreatic cancer [44], gastric cancer [45], and liver cancer [46], and it is associated with poor clinical prognosis. Disheveled (Dsh/Dvl) of the Wnt/β-catenin signaling pathway acts on FRAT1, allowing FRAT1 to compete with Axin to bind to the same site on glycogen synthase kinase-3β (GSK-3β), resulting in the separation of GSK-3β from the scaffold complex (mainly composed of APC, Axin, GSK-3β, and CK1), thereby inhibiting GSK-3β-mediated phosphorylation and degradation of β-catenin.…”

Section: Discussionmentioning

confidence: 99%

FRAT1 Enhances the Proliferation and Tumorigenesis of CD133⁺Nestin⁺ Glioma Stem Cells In Vitro and In Vivo

Guo¹,

Liu²,

Ren³

et al. 2020

J. Cancer

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Glioma stem cells (GSCs) are considered the source for development, recurrence, and poor prognosis of glioma, so treatment targeted GSCs is of great interest. The frequently rearranged in advanced T cell lymphomas-1 (FRAT1) gene is an important member of the Wnt/β-catenin signaling transduction pathway, and aberrantly activation of Wnt signaling has been identified to contribute to the tumorigenesis, proliferation, invasion of a variety kinds of cancer stem cells. However, correlations between FRAT1 and GSCs and the specific mechanisms remain unclear. In this study, we aimed to investigate the effect of FRAT1 on GSCs proliferation, colony formation, sphere formation and tumorigenesity in vitro and in vivo and its underlying mechanism. Lentiviral transfection was used to construct GSCs with low FRAT1 expression. The expression of FRAT1 on GSCs proliferation in vitro was assessed by cell counting kit-8(CCK-8). Colony formation and sphere formation assays were conducted to assess the colony and sphere formation ability of GSCs. Then, an intracranial glioma nude mouse model was built to measure the effect of low FRAT1 expression on GSCs proliferation and tumorigenesity in vivo. Real-time PCR, Western blot, and Immunohistochemistry were processed to detect the mRNA and protein expressions of FRAT1, β-catenin in the glioma tissue of xenograft mice to study their correlations. The functional assays verifed that low FRAT1 expression inhibited CD133 + Nestin + GSCs proliferation, colony formation, sphere formation ability in vitro. In vivo GSCs xenograft mice model showed that low FRAT1 expression suppressed the proliferation and tumorigenesity of CD133 + Nestin + GSCs and reduced β-catenin mRNA and protein expression. Furthermore, the expression of FRAT1 and β-catenin were positively correlated. Altogether, results indicate that FRAT1 enhances the proliferation, colony formation, sphere formation and tumorigenesity of CD133 + Nestin + glioma stem cells in vitro and in vivo as well as the expression of β-catenin. Therefore, inhibiting proliferation of GSCs and FRAT1 may be a molecular target to GSCs in treating human glioma in the future.

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Knockdown of FRAT1 inhibits hypoxia-induced epithelial-to-mesenchymal transition via suppression of the Wnt/β-catenin pathway in hepatocellular carcinoma cells

Cited by 15 publications

References 27 publications

LncRNA SNHG1 influences cell proliferation, migration, invasion, and apoptosis of non‐small cell lung cancer cells via the miR‐361‐3p/FRAT1 axis

LncRNA SNHG1 influences cell proliferation, migration, invasion, and apoptosis of non‐small cell lung cancer cells via the miR‐361‐3p/FRAT1 axis

Long non-coding RNA CCAT2 promotes epithelial-mesenchymal transition involving Wnt/β-catenin pathway in epithelial ovarian carcinoma cells

FRAT1 Enhances the Proliferation and Tumorigenesis of CD133⁺Nestin⁺ Glioma Stem Cells In Vitro and In Vivo

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Knockdown of FRAT1 inhibits hypoxia-induced epithelial-to-mesenchymal transition via suppression of the Wnt/β-catenin pathway in hepatocellular carcinoma cells

Cited by 15 publications

References 27 publications

LncRNA SNHG1 influences cell proliferation, migration, invasion, and apoptosis of non‐small cell lung cancer cells via the miR‐361‐3p/FRAT1 axis

LncRNA SNHG1 influences cell proliferation, migration, invasion, and apoptosis of non‐small cell lung cancer cells via the miR‐361‐3p/FRAT1 axis

Long non-coding RNA CCAT2 promotes epithelial-mesenchymal transition involving Wnt/β-catenin pathway in epithelial ovarian carcinoma cells

FRAT1 Enhances the Proliferation and Tumorigenesis of CD133+Nestin+ Glioma Stem Cells In Vitro and In Vivo

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FRAT1 Enhances the Proliferation and Tumorigenesis of CD133⁺Nestin⁺ Glioma Stem Cells In Vitro and In Vivo