LncRNA GAS5 is a critical regulator of metastasis phenotype of melanoma cells and inhibits tumor growth in vivo

Chen, Long; Yang, Huixin; Ye, Xiao; Tang, Xiaoxia; Li, Yuqian; Han, Qiaoqiao; Fu, Junping; Yang, Yuye; Zhu, Yuechun

doi:10.2147/ott.s98203

Cited by 47 publications

(48 citation statements)

References 71 publications

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“…Furthermore, it has been shown that demethylation of the MMP9 promoter region can facilitate MMP9 expression, which may be an essential factor in the occurrence and progression of DN . In our study, we discovered an inverse relationship between GAS5 and MMP9 expression, which is partially consistent with findings in a previous study that the gelatinolytic activity of MMP9 in melanoma cells was increased by siRNA‐mediated silencing of GAS5 . Furthermore, our study suggested that GAS5 was capable of recruiting EZH2 to the promoter region of MMP9, which drive H3K27me3, thus leading to downregulated MMP9 expression.…”

Section: Discussionsupporting

confidence: 91%

“…30 In our study, we discovered an inverse relationship between GAS5 and MMP9 expression, which is partially consistent with findings in a previous study that the gelatinolytic activity of MMP9 in melanoma cells was increased by siRNA-mediated silencing of GAS5. 31 Furthermore, our study suggested that GAS5 was capable of recruiting EZH2 to the promoter region of MMP9, which drive H3K27me3, thus leading to downregulated MMP9 expression. EZH2, a component of PRC2, is a histone H3K27 methyltransferase and plays a critical role in gene expression regulated by lncRNAs.…”

Section: Discussionmentioning

confidence: 70%

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Long noncoding RNA growth arrest‐specific transcript 5 alleviates renal fibrosis in diabetic nephropathy by downregulating matrix metalloproteinase 9 through recruitment of enhancer of zeste homolog 2

2020

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Diabetic nephropathy (DN) is a frequently occurred microvascular complication associated with type I and type II diabetes mellitus. The participation of long noncoding RNAs (lncRNAs) in diabetes-related microvascular complications has been reported extensively. We attempted to unveil the possible regulatory mechanism of lncRNA growth arrest-specific transcript 5 (GAS5) and matrix metalloproteinase 9 (MMP9), an important inflammatory protein, in the progression of DN. A rat DN model was induced by streptozocin (STZ). The low expression of GAS5 and high expression of MMP9 in DN rats with DN was then determined by RT-qPCR and western blot analysis, and lentivirus-mediated GAS5 overexpression was shown to ameliorate STZinduced renal interstitial fibrosis (RIF) and inflammatory reaction in the kidney of DN rats. Moreover, MMP9 was found to be upregulated in STZ-induced DN, while MMP9 silencing induced by lentivirus expressing shRNA against MMP9 reduced RIF and suppressed inflammation in the kidney of DN rats. RIP, RNA pull-down, and ChIP assays demonstrated that GAS5 downregulated MMP9 via recruiting enhancer of zeste homolog 2 (EZH2) in the promoter region of MMP9. Overall, our study reveals that GAS5 downregulates MMP9 expression through recruiting EZH2 to MMP9 promoter region and alleviates the progression of renal fibrosis in DN rats, which sheds new light on the therapeutic potential of GAS5-targeted therapies in combating that disease. K E Y W O R D Sdiabetic nephropathy, enhancer of zeste homolog 2, histone H3 methylated Lys27, long noncoding RNA growth arrest-specific transcript 5, matrix metalloproteinase 9, renal fibrosis

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 70%

Long noncoding RNA growth arrest‐specific transcript 5 alleviates renal fibrosis in diabetic nephropathy by downregulating matrix metalloproteinase 9 through recruitment of enhancer of zeste homolog 2

2020

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“…The current progress in the treatment of melanoma mainly remained focused on exploring the function of the immune system as well as the oncogenic driver mutations in melanoma [21]. Previous evidence has indicated the role of lncRNA GAS5 in the progression of melanoma, which could be the possible indicators for melanoma and could serve as a therapeutic target [22]. EZH2 [23], as well as CDKN1C [24], have also been recognized as promising biomarkers for treating melanoma.…”

Section: Discussionmentioning

confidence: 99%

Long non-coding RNA GAS5 accelerates oxidative stress in melanoma cells by rescuing EZH2-mediated CDKN1C downregulation

Yan

et al. 2020

Cancer Cell Int

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Background: The significance of long non-coding RNAs (lncRNAs) in mediating oxidative stress of cancers has been implicated recently. This study proposed a potential therapeutic target lncRNA growth arrest-specific transcript 5 (GAS5) for melanoma, due to its crucial role in oxidative stress and apoptosis of melanoma cells by regulating the enhancer of zeste homolog 2 (EZH2)-mediated CDKN1C expression. Methods: The lncRNA GAS5 expression pattern was examined in melanoma tissues and cells. The correlation of lncRNA GAS5, EZH2, and CDKN1C with survival rate of melanoma patients was analyzed. In melanoma cell lines, lncRNA GAS5 expression was overexpressed or knocked down to clarify its effects on cell viability, apoptosis, and oxidative stress. The interaction between lncRNA GAS5 and EZH2 was examined by RIP and RNA pull-down assays followed by verification of the target relationship between EZH2 and CDKN1C. Results: High expression of EZH2 and poor expression of lncRNA GAS5 and CDKN1C was observed in melanoma tissues and found to be correlated with the reduction in survival expectancy of melanoma patients. Overexpression of lncRNA GAS5 or CDKN1C or EZH2 knockdown could inhibit cell viability but enhance melanoma cell apoptosis and oxidative stress. Importantly, lncRNA GAS5 attenuated EZH2 expression by recruiting E2F4 to the EZH2 promoter region and knockdown of EZH2 upregulated CDKN1C expression by inhibiting the H3K27me3. Conclusion: The evidence provided by our study highlighted the involvement of lncRNA GAS5 in the translational suppression of EZH2 as well as the upregulation of CDKN1C, resulting in the promotion of melanoma cell apoptosis and oxidative stress.

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“…These etiologies are associated with varying clinical outcomes18 and affect chromosomes or protein-coding genes. The dysregulation of lncRNA expression has been linked to various diseases1920212223. However, studies of the roles of lncRNAs in neuroblastoma are lacking.…”

Section: Discussionmentioning

confidence: 99%

MEG3, HCN3 and linc01105 influence the proliferation and apoptosis of neuroblastoma cells via the HIF-1α and p53 pathways

Tang

Dong

et al. 2016

Sci Rep

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The purpose of this study was to investigate the differential expression and functional roles of long non-coding RNAs (lncRNAs) in neuroblastoma tissue. LncRNA microarrays were used to identify differentially expressed lncRNAs between tumor and para-tumor tissues. In total, in tumor tissues, 3,098 and 1,704 lncRNAs were upregulated and downregulated, respectively. HCN3 and linc01105 exhibited the higher expression (P < 0.05; P < 0.01, respectively) in neuroblastoma tissue, whereas MEG3 displayed the lower expression (P < 0.01). HIF-1α expression was negatively correlated with cell proliferation in the linc01105 KD group. In addition, Noxa and Bid expression was positively correlated with cell apoptosis. Moreover, linc01105 knockdown promoted cell proliferation, whereas MEG3 overexpression inhibited proliferation. Finally, linc01105 knockdown, MEG3 overexpression and HCN3 knockdown all increased apoptosis. The correlation coefficients between those three lncRNAs and the International Neuroblastoma Staging System (INSS) stage were −0.48, −0.58 and −0.55, respectively. In conclusion, we have identified lncRNAs that are differentially expressed in neuroblastoma tissues. The lncRNAs HCN3, linc01105, and MEG3 may be important in biological behaviors of neuroblastoma through mechanisms involving p53 pathway members such as HIF-1α, Noxa, and Bid. The expressions of MEG3, HCN3 and linc01105 are all negatively correlated with the INSS stage.

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LncRNA GAS5 is a critical regulator of metastasis phenotype of melanoma cells and inhibits tumor growth in vivo

Cited by 47 publications

References 71 publications

Long noncoding RNA growth arrest‐specific transcript 5 alleviates renal fibrosis in diabetic nephropathy by downregulating matrix metalloproteinase 9 through recruitment of enhancer of zeste homolog 2

Long noncoding RNA growth arrest‐specific transcript 5 alleviates renal fibrosis in diabetic nephropathy by downregulating matrix metalloproteinase 9 through recruitment of enhancer of zeste homolog 2

Long non-coding RNA GAS5 accelerates oxidative stress in melanoma cells by rescuing EZH2-mediated CDKN1C downregulation

MEG3, HCN3 and linc01105 influence the proliferation and apoptosis of neuroblastoma cells via the HIF-1α and p53 pathways

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