Long non-coding RNA UCA1 regulates the expression of Snail2 by miR-203 to promote hepatocellular carcinoma progression

J, Xiao; Yan, Tinghua; Yu, Rui-Ming; Gao, Yi; Zeng, Wenlong; Lu, Sui-Wan; Que, Hua-Xing; Liu, Zeping; Jiang, Jinhua

doi:10.1007/s00432-017-2370-1

Cited by 86 publications

(84 citation statements)

References 25 publications

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“…Slug has been confirmed as the downstream effector of TGF-b signaling pathway; here, we indicated that lncRNA UCA1 served as the downstream effector of TGF-b and the upstream effector of Slug, respectively, which is consistent with recent studies in other cancers [14,19,20]. Thus, we wonder whether the TGF-b-UCA1-Slug regulatory axis is a common phenomenon in cancers.…”

Section: Discussionsupporting

confidence: 89%

LncRNA UCA1 is necessary for TGF‐β‐induced epithelial–mesenchymal transition and stemness via acting as a ceRNA for Slug in glioma cells

Liu

Zhong

et al. 2018

FEBS Open Bio

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The 5‐year survival rate of patients with glioma is < 5%, and therefore there is an urgent need to find novel potential targets for facilitating its diagnosis and treatment. The long non‐coding RNA (lnc RNA ) UCA 1 has been shown to promote the proliferation and invasion of cervical cancer cells through regulating miR‐206 expression, but the involvement of UCA 1 in regulating the stemness and epithelial–mesenchymal transition ( EMT ) of glioma cells is unknown. Here, we report that the expression of UCA 1 is significantly increased by transforming growth factor‐β ( TGF ‐β) treatment in glioma cells and is greater in glioma tissues than in normal adjacent tissues. Additionally, TGF ‐β induced EMT and the stemness of glioma cells, whereas knockdown of lnc RNA UCA 1 attenuated these two processes and their enhancement by TGF ‐β. Mechanistically, knockdown of UCA 1 decreased Slug expression by acting as a competitive endogenous RNA (ce RNA ) through competitive binding with miR‐1 and miR‐203a; this effect was further evidenced by the fact that transfection with miR‐1 or miR‐203a inhibitors abrogated the effects of UCA 1 knockdown on Slug expression, and UCA 1 colocalized with miR‐1 and miR‐203a in glioma tissues. Notably, ectopic expression of Slug rescued the attenuation of UCA 1 knockdown on EMT and the stemness of glioma cells. These results indicate that UCA 1 may act as a ce RNA to promote Slug expression, which underlies TGF ‐β‐induced EMT and stemness of glioma cells.

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Section: Discussionsupporting

confidence: 89%

LncRNA UCA1 is necessary for TGF‐β‐induced epithelial–mesenchymal transition and stemness via acting as a ceRNA for Slug in glioma cells

Liu

Zhong

et al. 2018

FEBS Open Bio

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“…As a novel regulatory mechanism, lncRNAs act as an endogenous ceRNA or sponge for miRNAs to regulate the degradation of miRNA targets . For example, UCA1 overexpression promoted epithelial‐mesenchymal transition (EMT) in hepatocellular carcinoma via effectively sponging miR‐203 and thereby activating the expression of transcription factor Snail2, a target of miR‐203 . UCA1 upregulation enhanced tamoxifen resistance in breast cancer cells through a miR‐18a‐HIF1α feedback loop .…”

Section: Discussionmentioning

confidence: 99%

Knockdown of LncRNA‐UCA1 suppresses chemoresistance of pediatric AML by inhibiting glycolysis through the microRNA‐125a/hexokinase 2 pathway

Zhang

Liu

2018

J of Cellular Biochemistry

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Dysregulation of lncRNAs is implicated in chemoresistance in varieties of tumor including acute myeloid leukemia (AML). LncRNA urothelial carcinoma-associated 1 (UCA1) was reported to play an oncogenic role in AML. However, whether UCA1 was involved in chemoresistance in pediatric AML remains unclear. UCA1 expression in AML patients after adriamycin (ADR)-based chemotherapy and ADR-resistant AML cells was examined by qRT-PCR. The effects of UCA1 on the cytotoxicity of ADR and glycolysis were evaluated by MTT assay and measuring the glucose consumption and lactate production in HL60 and HL60/ADR cells, repectively. The protein levels of hypoxia-inducible factor 1α (HIF-1α) and hexokinase 2 (HK2) were determined by Western blot. Luciferase reporter assay and RNA immunoprecipitation (RIP) assay were used to confirm the relationships between UCA1, HK2, and miR-125a. We found that UCA1 expression was upregulated following ADR-based chemotherapy. Knockdown of UCA1 increased the cytotoxic effect of ADR and inhibited HIF-1α-dependent glycolysis in ADR-resistant AML cells. Additionally, UCA1 functioned as a ceRNA of miR-125a by directly binding to miR-125a. HK2, a target of miR-125a, was positively regulated by UCA1 in HL60 and HL60/ADR cells. More notably, UCA1 overexpression overturned miR-125-mediated inhibition on HIF-1α-dependent glycolysis in HL60 and HL60/ADR cells. Furthermore, 2-deoxy-glucose (2-DG) exposure inhibited HIF-1α-dependent glycolysis, and attenuated UCA1-induced increase of chemoresistance in HL60 and HL60/ADR cells. We conclude that knockdown of UCA1 plays a positive role in overcoming the chemoresistance of pediatric AML, through suppressing glycolysis by the miR-125a/HK2 pathway, contributing to a better understanding of the molecular mechanism of chemoresistance in AML.

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“…Based on its their reported functionality, demonstrated target genes and expression pattern during chick development (Darnell et al, 2006), we further focused on miR-203 for in depth analysis. Importantly, miR-203 has been described to act as tumor suppressor (Benaich et al, 2014, Miao et al, 2014, Zhu et al, 2013b), that directly regulates Snail2 expression (Gao et al, 2017, Shi et al, 2015, Zhang et al, 2015, Xiao et al, 2017), whose epigenetic repression causes metastasis in several tumor cells including NCC-derived melanoma (Boldrup et al, 2012, Boll et al, 2013, Chen et al, 2012, Chiang et al, 2011, Ding et al, 2013, Furuta et al, 2010, Huang et al, 2014, Ju et al, 2014, Moes et al, 2012, Zhang et al, 2014, Zhao et al, 2013, Bu and Yang, 2014, Lohcharoenkal et al, 2018). Moreover, the mature miR-203 sequence is highly conserved throughout vertebrates including the basal lamprey (Fig.…”

Section: Resultsmentioning

confidence: 99%

Epigenetic inactivation of miR-203 as a key step in neural crest epithelial-to-mesenchymal transition

Sánchez-Vásquez

Bronner

Strobl-Mazzulla

2018

Preprint

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AbstractmiR-203 is a tumor-suppressor microRNA with known functions in cancer metastasis. Here, we explore its normal developmental role in the context of neural crest development. As neural crest cells undergo an epithelial-to-mesenchymal transition to emigrate from the neural tube, miR-203 displays a reciprocal expression pattern with key regulators of neural crest delamination, Phf12 and Snail2, and interacts with their 3’UTRs. Ectopic maintenance of miR-203 inhibits neural crest migration, whereas its functional inhibition using a “sponge” vector promotes premature neural crest delamination. Bisulfite sequencing further shows that epigenetic repression of miR-203 is mediated by the de novo DNA methyltransferase DNMT3B, whose recruitment to regulatory regions on the miR-203 locus is directed by SNAIL2 in a negative feedback loop. These findings reveal an important role for miR-203 in an epigenetic-microRNA regulatory network that influences the timing of neural crest delamination.Summary statementThe EMT is a highly conserved process, involving similar levels of regulation in both neural crest and cancer cells. Our work shows an epigenetic-miRNA-gene regulatory circuit, conserved in cancer, which controls the timing of neural crest EMT as well.

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Long non-coding RNA UCA1 regulates the expression of Snail2 by miR-203 to promote hepatocellular carcinoma progression

Abstract: Our results identified that UCA1/miR-203/Snail2 pathway might involve in HCC progression. Inhibition of UCA1 acted as a promising therapeutic target for HCC patients.

Cited by 86 publications

References 25 publications

LncRNA UCA1 is necessary for TGF‐β‐induced epithelial–mesenchymal transition and stemness via acting as a ceRNA for Slug in glioma cells

LncRNA UCA1 is necessary for TGF‐β‐induced epithelial–mesenchymal transition and stemness via acting as a ceRNA for Slug in glioma cells

Knockdown of LncRNA‐UCA1 suppresses chemoresistance of pediatric AML by inhibiting glycolysis through the microRNA‐125a/hexokinase 2 pathway

Epigenetic inactivation of miR-203 as a key step in neural crest epithelial-to-mesenchymal transition

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