Silencing of microRNA-708 promotes cell growth and epithelial-to-mesenchymal transition by activating the SPHK2/AKT/β-catenin pathway in glioma

Chen, Yan; Deng, Xubin; Chen, Weiquan; Shi, Pengwei; Mei, Lian; Wang, Hongxiao; Wang, Kewan; Qian, Dadi; Xiao, Dong; Long, Hao

doi:10.1038/s41419-019-1671-5

Cited by 31 publications

(28 citation statements)

References 53 publications

(55 reference statements)

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“…miRNAs can regulate gene expression through binding to the 3ʹ untranslated regions (3ʹUTRs) of RNA transcripts, resulting in mRNA degradation or translation inhibition. Several studies have revealed that miRNAs could be pivotal regulators of tumor suppressors or oncogenes 4,5. In addition, miRNAs could also play vital role in various biological processes such as cell proliferation, apoptosis and the cell cycle 6.…”

Section: Introductionmentioning

confidence: 99%

miR-140-3p Suppresses Cell Growth And Induces Apoptosis In Colorectal Cancer By Targeting PD-L1

Jiang¹,

Li²,

Wang³

et al. 2019

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BackgroundA variety of miRNAs have been recently reported to be abnormally expressed in colorectal cancer (CRC). A growing number of studies have demonstrated that aberrantly expressed miRNAs are closely related to the development and progression of CRC. It has been found that miR-140-3p plays a vital role in several cancers. However, its expression, roles and mechanisms in CRC are remain unknown.Materials and methodsReverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to determine miR-140-3p expression in CRC tissues and cell lines. CCK8, migration, invasion and flow cytometric assays were used to determine the influence of miR-140-3p upregulation on cell proliferation, migration, invasion and apoptosis of CRC cells. Luciferase reporter assays and Western blots were utilized to identify the target genes of miR-140-3p. In addition, the potential mechanism of miR-140-3p action in CRC cells was elucidated.ResultsIn our study, miR-140-3p expression was significantly decreased in CRC tissues and cell lines. Overexpression of miR-140-3p attenuated proliferation, migration, and invasion and induced the apoptosis of CRC cells. Bioinformatics analyse and luciferase reporter analysis identified PD-L1 as a putative target gene of miR-140-3p. PD-L1 was overexpressed in CRC tissues and inversely correlated with miR-140-3p expression. Suppression of PD-L1 expression in CRC cells generated biological behaviours in CRC cells that were similar to those observed after treated with miR-140-3p mimics. Restoration of PD-L1 expression partially attenuated the inhibitory effect of miR-140-3p on CRC cells. Western blot were used to verify the effect of PD-L1 expression on PI3K/AKT pathway. In addition, overexpression of miR-140-3p could inhibit CRC tumor growth in vivo.ConclusionIn general, these data demonstrate that miR-140-3p acts as a tumour suppressor in CRC by directly targeting PD-L1 and inactivating PI3K/AKT pathway, suggesting that miR-140-3p might be a novel target for CRC diagnosis and treatment.

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Section: Introductionmentioning

confidence: 99%

miR-140-3p Suppresses Cell Growth And Induces Apoptosis In Colorectal Cancer By Targeting PD-L1

Jiang¹,

Li²,

Wang³

et al. 2019

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“…In gliomas, miRNAs are crucial regulators in the tumorigenesis and tumor progression 12. The expression of miR-708 is down-regulated in glioma tissues and it suppresses the growth and epithelial-to-mesenchymal transition (EMT) of glioma cells by targeting sphingosine kinase 2 (SPHK2)-mediated AKT/β-catenin pathway 13. miR-4500 functions as a tumor suppressor by attenuating insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) in glioma cells 14.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-769-5p Promotes The Growth Of Glioma Cells By Targeting Lysine Methyltransferase 2A

Chang¹,

Peng²,

Zhang³

et al. 2019

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BackgroundAccumulating evidence supports the involvement of microRNAs (miRNAs) in the progression of human cancers including glioma. Recently, miR-769-5p has been reported to play a tumor suppressive role in colorectal cancer and lung cancer, whereas it exerts an oncogenic role in melanoma. However, the role of miR-769-5p and its related mechanism are poorly elucidated.MethodsThe levels of miR-769-5p in glioma tissues and adjacent non-tumor tissues were detected by qRT-PCR. In addition, the effects of miR-769-5p on cell proliferation and apoptosis were evaluated by CCK-8, EdU, colony formation and flow cytometric assays, respectively. Meanwhile, the dual-luciferase reporter assay was used to investigate the interaction of miR-769-5p and lysine methyltransferase 2A (KMT2A) in glioma.ResultsWe found that miR-769-5p expression was strongly upregulated in glioma tissues and cell lines. Glioma tissues with high World Health Organization (WHO) grades had obvious higher levels of miR-769-5p compared to samples with low WHO grades. Interestingly, glioma patients highly expressing miR-769-5p showed prominent poorer survivals. Knockdown of miR-769-5p significantly suppressed cell proliferation and resulted in apoptosis in glioma cells. Additionally, miR-769-5p silencing restrained in vivo growth of glioma cells in mice. Interestingly, KMT2A was identified to be a direct target of miR-769-5p in glioma cells. The expression of KMT2A mRNA was downregulated in glioma tissues and inversely correlated with miR-769-5p level. KMT2A overexpression inhibited cell proliferation and induced the apoptosis of A172 cells. Moreover, siRNA-mediated KMT2A silencing could partially abolish miR-769-5p knockdown-induced suppressive effects on A172 cells.ConclusionIn summary, our findings suggest that targeting miR-769-5p/KMT2A axis may be a promising therapeutic target for glioma treatment.

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“…Accumulating evidence shows that nuclear accumulation of β-catenin play crucial role in regulating EMT [ 33 , 34 ]. Recently, Dong Xiao et al found that SPHK2, a direct target of miR-708, triggered a cascade of signals leading to the activation of Akt pathway and the phosphorylation of GSK-3β and finally to the nuclear translocation of β-catenin to regulate EMT in glioma cells [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

Hypoxia induced ferritin light chain (FTL) promoted epithelia mesenchymal transition and chemoresistance of glioma

Liu

Gao

Zhan

et al. 2020

J Exp Clin Cancer Res

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Background Hypoxia, a fundamental characteristic of glioma, is considered to promote tumor malignancy by inducing process of epithelial mesenchymal transition (EMT). Ferritin Light Chain (FTL) is one of the iron metabolism regulators and is overexpressed in glioma. However, relationship between hypoxia and FTL expression and its role in regulating EMT remains unclear. Methods Immunohistochemistry (IHC), western blot and public datasets were used to evaluate FTL level in glioma. Wound healing, transwell assays, CCK8, annexin V staining assay were used to measure migration, invasion, proliferation and apoptosis of glioma cells in vitro. Interaction between HIF1A and FTL was assessed by luciferase reporter and Chromatin immunoprecipitation (ChIP) assays. Subcutaneous xenograft model was established to investigate in vivo growth. Results FTL expression was enriched in high grade glioma (HGG) and its expression significantly associated with IDH1/2 wildtype and unfavorable prognosis of glioma patients. FTL expression positively correlated with HIF1A in glioma tissues and obviously increased in U87 and U251 cells under hypoxia in a time-dependent manner. Mechanistically, HIF-1α regulates FTL expression by directly binding to HRE-3 in FTL promoter region. Furthermore, we found that knockdown FTL dramatically repressed EMT and reduced migration and invasion of glioma by regulating AKT/GSK3β/ β-catenin signaling both in vitro and in vivo. Moreover, our study found downregulation FTL decreased the survival rate and increased the apoptosis of glioma cells treated with temozolomide (TMZ). FTL expression segregated glioma patients who were treated with TMZ or with high MGMT promoter methylation into survival groups in TCGA dataset. Patients with methylated MGMT who had high FTL expression presented similar prognosis with patients with unmethylated MGMT. Conclusion Our study strongly suggested that hypoxia-inducible FTL was a regulator of EMT and acted not only as a prognostic marker but also a novel biomarker of response to TMZ in glioma.

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Silencing of microRNA-708 promotes cell growth and epithelial-to-mesenchymal transition by activating the SPHK2/AKT/β-catenin pathway in glioma

Cited by 31 publications

References 53 publications

<p>miR-140-3p Suppresses Cell Growth And Induces Apoptosis In Colorectal Cancer By Targeting PD-L1</p>

<p>miR-140-3p Suppresses Cell Growth And Induces Apoptosis In Colorectal Cancer By Targeting PD-L1</p>

<p>MicroRNA-769-5p Promotes The Growth Of Glioma Cells By Targeting Lysine Methyltransferase 2A</p>

Hypoxia induced ferritin light chain (FTL) promoted epithelia mesenchymal transition and chemoresistance of glioma

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