We are analyzing https://link.springer.com/article/10.1186/s12943-022-01638-1.

Title:
Hypoxia-induced lncRNA STEAP3-AS1 activates Wnt/β-catenin signaling to promote colorectal cancer progression by preventing m6A-mediated degradation of STEAP3 mRNA | Molecular Cancer
Description:
Background Hypoxia, a typical hallmark of solid tumors, exhibits an essential role in the progression of colorectal cancer (CRC), in which the dysregulation of long non-coding RNAs (lncRNAs) is frequently observed. However, the underlying mechanisms are not clearly defined. Methods The TCGA database was analyzed to identify differential lncRNA expression involved in hypoxia-induced CRC progression. qRT-PCR was conducted to validate the upregulation of lncRNA STEAP3-AS1 in CRC cell lines and tumor-bearing mouse and zebrafish models under hypoxia. ChIP-qRT-PCR was used to detect the transcriptional activation of STEAP3-AS1 mediated by HIF-1α. RNA-seq, fluorescent in situ hybridization, RNA pulldown, RNA immunoprecipitation, co-immunoprecipitation, immunofluorescence and immunoblot experiments were used to ascertain the involved mechanisms. Functional assays were performed in both in vitro and in vivo models to investigate the regulatory role of STEAP3-AS1/STEAP3/Wnt/β-catenin axis in CRC proliferation and metastasis. Results Here, we identified a hypoxia-induced antisense lncRNA STEAP3-AS1 that was highly expressed in clinical CRC tissues and positively correlated with poor prognosis of CRC patients. Upregulation of lncRNA STEAP3-AS1, which was induced by HIF-1α-mediated transcriptional activation, facilitated the proliferation and metastasis of CRC cells both in vitro and in vivo. Mechanistically, STEAP3-AS1 interacted competitively with the YTH domain-containing family protein 2 (YTHDF2), a N6-methyladenosine (m6A) reader, leading to the disassociation of YTHDF2 with STEAP3 mRNA. This effect protected STEAP3 mRNA from m6A-mediated degradation, enabling the high expression of STEAP3 protein and subsequent production of cellular ferrous iron (Fe2+). Increased Fe2+ levels elevated Ser 9 phosphorylation of glycogen synthase kinase 3 beta (GSK3β) and inhibited its kinase activity, thus releasing β-catenin for nuclear translocation and subsequent activation of Wnt signaling to support CRC progression. Conclusions Taken together, our study highlights the mechanisms of lncRNA STEAP3-AS1 in facilitating CRC progression involving the STEAP3-AS1/STEAP3/Wnt/β-catenin axis, which may provide novel diagnostic biomarkers or therapeutic targets to benefit CRC treatment. Graphical abstract Hypoxia-induced HIF-1α transcriptionally upregulates the expression of lncRNA STEAP3-AS1, which interacts competitively with YTHDF2, thus upregulating mRNA stability of STEAP3 and consequent STEAP3 protein expression. The enhanced STEAP3 expression results in production of cellular ferrous iron (Fe2+), which induces the Ser 9 phosphorylation and inactivation of GSK3β, releasing β-catenin for nuclear translocation and contributing to subsequent activation of Wnt signaling to promote CRC progression.
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Keywords {🔍}

steapas, cells, crc, pubmed, steap, fig, cancer, dld, article, google, scholar, lncrna, rna, expression, cas, progression, knockdown, shsteapas, cell, control, analysis, mrna, assay, central, data, signaling, ythdf, cat, gskβ, hypoxia, relative, overexpression, proliferation, protein, metastasis, scale, bar, performed, migration, level, lncrnas, antisense, levels, steapasknockdown, wntβcatenin, assays, βcatenin, hifα, results, dilution,

Topics {✒️}

steap3-as1/steap3/wnt/β-catenin axis steap3-as1/wnt/β-catenin axis steap3/gsk3β/wnt/β-catenin axis stimulate wnt/β-catenin signaling wnt/β-catenin signaling relies activated wnt/β-catenin signaling activating wnt/β-catenin signaling steap3-as1/steap3-mediated fe2+ generation enhance rac1-erk-stat3 signaling hypoxia-induced lncrna steap3-as1 wnt/β-catenin signaling lncrna hoxd-as1 mediated steap3-as1-mediated crc progression steap3-as1-induced crc progression steap3-as1-induced crc proliferation activate wnt/β-catenin hypoxia-induced epithelial-mesenchymal transition steap3-as1-overexpressing crc cells β-catenin/axin/gsk3β complex steap3-as1-overexpressing hct116 cells article download pdf steap3-as1-knockdown crc cells m6a modification-dependent manner steap3-mediated fe2+ generation steap3-as1-knockdown dld-1 cells hypoxia-induced alternative splicing preventing m6a-mediated degradation prevent m6a-mediated degradation inhibit m6a-mediated degradation prevented m6a-mediated degradation steap3-as1-knockdown sw480 cells hif-1α-mediated transcriptional activation lncrna steap3-as1 increases lncrna steap3-as1 knockdown top/fop flash assay hai-ning chen lncrna steap3-as1 interacted hypoxia-inducible factor biology m6a-mediated mrna decay hypoxia-induced crc progression sirna-mediated steap3 knockdown explaining hypoxia-promoted crc hypoxia-promoted tumor progression steap3-as1-knockdown resulted steap3-as1 knockdown resulted steap3-as1 knockdown hindered lncrna steap3-as1 decreased strept avidin-biotin complex wnt signaling pathway mettl14-mediated m6a modification

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         headline:Hypoxia-induced lncRNA STEAP3-AS1 activates Wnt/β-catenin signaling to promote colorectal cancer progression by preventing m6A-mediated degradation of STEAP3 mRNA
         description:Hypoxia, a typical hallmark of solid tumors, exhibits an essential role in the progression of colorectal cancer (CRC), in which the dysregulation of long non-coding RNAs (lncRNAs) is frequently observed. However, the underlying mechanisms are not clearly defined. The TCGA database was analyzed to identify differential lncRNA expression involved in hypoxia-induced CRC progression. qRT-PCR was conducted to validate the upregulation of lncRNA STEAP3-AS1 in CRC cell lines and tumor-bearing mouse and zebrafish models under hypoxia. ChIP-qRT-PCR was used to detect the transcriptional activation of STEAP3-AS1 mediated by HIF-1α. RNA-seq, fluorescent in situ hybridization, RNA pulldown, RNA immunoprecipitation, co-immunoprecipitation, immunofluorescence and immunoblot experiments were used to ascertain the involved mechanisms. Functional assays were performed in both in vitro and in vivo models to investigate the regulatory role of STEAP3-AS1/STEAP3/Wnt/β-catenin axis in CRC proliferation and metastasis. Here, we identified a hypoxia-induced antisense lncRNA STEAP3-AS1 that was highly expressed in clinical CRC tissues and positively correlated with poor prognosis of CRC patients. Upregulation of lncRNA STEAP3-AS1, which was induced by HIF-1α-mediated transcriptional activation, facilitated the proliferation and metastasis of CRC cells both in vitro and in vivo. Mechanistically, STEAP3-AS1 interacted competitively with the YTH domain-containing family protein 2 (YTHDF2), a N6-methyladenosine (m6A) reader, leading to the disassociation of YTHDF2 with STEAP3 mRNA. This effect protected STEAP3 mRNA from m6A-mediated degradation, enabling the high expression of STEAP3 protein and subsequent production of cellular ferrous iron (Fe2+). Increased Fe2+ levels elevated Ser 9 phosphorylation of glycogen synthase kinase 3 beta (GSK3β) and inhibited its kinase activity, thus releasing β-catenin for nuclear translocation and subsequent activation of Wnt signaling to support CRC progression. Taken together, our study highlights the mechanisms of lncRNA STEAP3-AS1 in facilitating CRC progression involving the STEAP3-AS1/STEAP3/Wnt/β-catenin axis, which may provide novel diagnostic biomarkers or therapeutic targets to benefit CRC treatment. Hypoxia-induced HIF-1α transcriptionally upregulates the expression of lncRNA STEAP3-AS1, which interacts competitively with YTHDF2, thus upregulating mRNA stability of STEAP3 and consequent STEAP3 protein expression. The enhanced STEAP3 expression results in production of cellular ferrous iron (Fe2+), which induces the Ser 9 phosphorylation and inactivation of GSK3β, releasing β-catenin for nuclear translocation and contributing to subsequent activation of Wnt signaling to promote CRC progression.
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            Hypoxia
            LncRNA STEAPS-AS1
            STEAP3
            m6A modification
            YTHDF2
            Wnt/β-catenin
            Colorectal cancer
            Cancer Research
            Oncology
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      headline:Hypoxia-induced lncRNA STEAP3-AS1 activates Wnt/β-catenin signaling to promote colorectal cancer progression by preventing m6A-mediated degradation of STEAP3 mRNA
      description:Hypoxia, a typical hallmark of solid tumors, exhibits an essential role in the progression of colorectal cancer (CRC), in which the dysregulation of long non-coding RNAs (lncRNAs) is frequently observed. However, the underlying mechanisms are not clearly defined. The TCGA database was analyzed to identify differential lncRNA expression involved in hypoxia-induced CRC progression. qRT-PCR was conducted to validate the upregulation of lncRNA STEAP3-AS1 in CRC cell lines and tumor-bearing mouse and zebrafish models under hypoxia. ChIP-qRT-PCR was used to detect the transcriptional activation of STEAP3-AS1 mediated by HIF-1α. RNA-seq, fluorescent in situ hybridization, RNA pulldown, RNA immunoprecipitation, co-immunoprecipitation, immunofluorescence and immunoblot experiments were used to ascertain the involved mechanisms. Functional assays were performed in both in vitro and in vivo models to investigate the regulatory role of STEAP3-AS1/STEAP3/Wnt/β-catenin axis in CRC proliferation and metastasis. Here, we identified a hypoxia-induced antisense lncRNA STEAP3-AS1 that was highly expressed in clinical CRC tissues and positively correlated with poor prognosis of CRC patients. Upregulation of lncRNA STEAP3-AS1, which was induced by HIF-1α-mediated transcriptional activation, facilitated the proliferation and metastasis of CRC cells both in vitro and in vivo. Mechanistically, STEAP3-AS1 interacted competitively with the YTH domain-containing family protein 2 (YTHDF2), a N6-methyladenosine (m6A) reader, leading to the disassociation of YTHDF2 with STEAP3 mRNA. This effect protected STEAP3 mRNA from m6A-mediated degradation, enabling the high expression of STEAP3 protein and subsequent production of cellular ferrous iron (Fe2+). Increased Fe2+ levels elevated Ser 9 phosphorylation of glycogen synthase kinase 3 beta (GSK3β) and inhibited its kinase activity, thus releasing β-catenin for nuclear translocation and subsequent activation of Wnt signaling to support CRC progression. Taken together, our study highlights the mechanisms of lncRNA STEAP3-AS1 in facilitating CRC progression involving the STEAP3-AS1/STEAP3/Wnt/β-catenin axis, which may provide novel diagnostic biomarkers or therapeutic targets to benefit CRC treatment. Hypoxia-induced HIF-1α transcriptionally upregulates the expression of lncRNA STEAP3-AS1, which interacts competitively with YTHDF2, thus upregulating mRNA stability of STEAP3 and consequent STEAP3 protein expression. The enhanced STEAP3 expression results in production of cellular ferrous iron (Fe2+), which induces the Ser 9 phosphorylation and inactivation of GSK3β, releasing β-catenin for nuclear translocation and contributing to subsequent activation of Wnt signaling to promote CRC progression.
      datePublished:2022-08-19T00:00:00Z
      dateModified:2022-08-19T00:00:00Z
      pageStart:1
      pageEnd:22
      license:http://creativecommons.org/publicdomain/zero/1.0/
      sameAs:https://doi.org/10.1186/s12943-022-01638-1
      keywords:
         Hypoxia
         LncRNA STEAPS-AS1
         STEAP3
         m6A modification
         YTHDF2
         Wnt/β-catenin
         Colorectal cancer
         Cancer Research
         Oncology
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                     name:State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Basic Sciences & Forensic Medicine, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, P.R. China
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