
DOI . ORG {
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Title[redir]:
m6A-induced lncRNA RP11 triggers the dissemination of colorectal cancer cells via upregulation of Zeb1 | Molecular Cancer | Full Text
Description:
Background Long noncoding RNAs (lncRNAs) have emerged as critical players in cancer progression, but their functions in colorectal cancer (CRC) metastasis have not been systematically clarified. Methods lncRNA expression profiles in matched normal and CRC tissue were checked using microarray analysis. The biological roles of a novel lncRNA, namely RP11-138โJ23.1 (RP11), in development of CRC were checked both in vitro and in vivo. Its association with clinical progression of CRC was further analyzed. Results RP11 was highly expressed in CRC tissues, and its expression increased with CRC stage in patients. RP11 positively regulated the migration, invasion and epithelial mesenchymal transition (EMT) of CRC cells in vitro and enhanced liver metastasis in vivo. Post-translational upregulation of Zeb1, an EMT-related transcription factor, was essential for RP11-induced cell dissemination. Mechanistically, the RP11/hnRNPA2B1/mRNA complex accelerated the mRNA degradation of two E3 ligases, Siah1 and Fbxo45, and subsequently prevented the proteasomal degradation of Zeb1. m6A methylation was involved in the upregulation of RP11 by increasing its nuclear accumulation. Clinical analysis showed that m6A can regulate the expression of RP11, further, RP11 regulated Siah1-Fbxo45/Zeb1 was involved in the development of CRC. Conclusions m6A-induced lncRNA RP11 can trigger the dissemination of CRC cells via post-translational upregulation of Zeb1. Considering the high and specific levels of RP11 in CRC tissues, our present study paves the way for further investigations of RP11 as a predictive biomarker or therapeutic target for CRC.
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Keywords {๐}
cells, crc, expression, hct, zeb, cancer, fig, article, overexpression, siah, analysis, fbxo, figure, scholar, rna, additional, google, file, control, cell, cas, data, tissues, mrna, stage, levels, patients, lncrnas, hnrnpab, lncrna, stable, normal, progression, metastasis, emt, colorectal, showed, upregulation, wang, protein, tumour, dissemination, significant, significantly, effect, noncoding, chen, long, stability, colon,
Topics {โ๏ธ}
hnrnpa2b1/nf-kappab pathway rp11/hnrnpa2b1/mrna complex accelerated sun yat-sen university beta-catenin-dependent regulation rp11-hnrnpa2b1-mrna complex downregulates t7/sp6 rna polymerase m6a/rp11/zeb1 axis triggers rna n6-methyladenosine methyltransferase n6-methyladenosine rna demethylase poly a-tailed due post-transcriptional gene regulation long noncoding rnas includes multi-omics data analyzing multi-omics data inhibit e-cadherin expression final concentration 100โฮผg/ml broad-spectrum hdac inhibitors promote epithelial-mesenchymal transition ubiquitin ligase siah rna-rna interactions rp11-hnrnpa2b1-mrna complex rp11-induced cell dissemination noncoding rna mapping m6a methylation-regulated rp11 generate biotin-labelled rp-11 privacy choices/manage cookies mesc differentiation potential emt-inducing transcription factors m6a/rp11/zeb1 axis lncrna rp11-induced emt protein-rna interactions lncrna lnchc-binding hnrnpa2b1 specific protein interacting rp11 regulated siah1-fbxo45/zeb1 state key laboratory sds-page cover page authors scientific editing pgem-t-rp11 vector rp11-overexpressing hct-15 cells bmc tgf-beta promotes m6a rip-qpcr analysis ubiquitin e3 ligases m6a-dependent model qubitยฎ rna high-sensitivity rp11-regulated mrna expression distinguished young scholar collaborative innovation center kaplan-meier plotter
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headline:m6A-induced lncRNA RP11 triggers the dissemination of colorectal cancer cells via upregulation of Zeb1
description:Long noncoding RNAs (lncRNAs) have emerged as critical players in cancer progression, but their functions in colorectal cancer (CRC) metastasis have not been systematically clarified. lncRNA expression profiles in matched normal and CRC tissue were checked using microarray analysis. The biological roles of a novel lncRNA, namely RP11-138โJ23.1 (RP11), in development of CRC were checked both in vitro and in vivo. Its association with clinical progression of CRC was further analyzed. RP11 was highly expressed in CRC tissues, and its expression increased with CRC stage in patients. RP11 positively regulated the migration, invasion and epithelial mesenchymal transition (EMT) of CRC cells in vitro and enhanced liver metastasis in vivo. Post-translational upregulation of Zeb1, an EMT-related transcription factor, was essential for RP11-induced cell dissemination. Mechanistically, the RP11/hnRNPA2B1/mRNA complex accelerated the mRNA degradation of two E3 ligases, Siah1 and Fbxo45, and subsequently prevented the proteasomal degradation of Zeb1. m6A methylation was involved in the upregulation of RP11 by increasing its nuclear accumulation. Clinical analysis showed that m6A can regulate the expression of RP11, further, RP11 regulated Siah1-Fbxo45/Zeb1 was involved in the development of CRC. m6A-induced lncRNA RP11 can trigger the dissemination of CRC cells via post-translational upregulation of Zeb1. Considering the high and specific levels of RP11 in CRC tissues, our present study paves the way for further investigations of RP11 as a predictive biomarker or therapeutic target for CRC.
datePublished:2019-04-13T00:00:00Z
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LncRNA RP11
CRC
Zeb1
m6A
hnRNPA2B1
Cell dissemination
Cancer Research
Oncology
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headline:m6A-induced lncRNA RP11 triggers the dissemination of colorectal cancer cells via upregulation of Zeb1
description:Long noncoding RNAs (lncRNAs) have emerged as critical players in cancer progression, but their functions in colorectal cancer (CRC) metastasis have not been systematically clarified. lncRNA expression profiles in matched normal and CRC tissue were checked using microarray analysis. The biological roles of a novel lncRNA, namely RP11-138โJ23.1 (RP11), in development of CRC were checked both in vitro and in vivo. Its association with clinical progression of CRC was further analyzed. RP11 was highly expressed in CRC tissues, and its expression increased with CRC stage in patients. RP11 positively regulated the migration, invasion and epithelial mesenchymal transition (EMT) of CRC cells in vitro and enhanced liver metastasis in vivo. Post-translational upregulation of Zeb1, an EMT-related transcription factor, was essential for RP11-induced cell dissemination. Mechanistically, the RP11/hnRNPA2B1/mRNA complex accelerated the mRNA degradation of two E3 ligases, Siah1 and Fbxo45, and subsequently prevented the proteasomal degradation of Zeb1. m6A methylation was involved in the upregulation of RP11 by increasing its nuclear accumulation. Clinical analysis showed that m6A can regulate the expression of RP11, further, RP11 regulated Siah1-Fbxo45/Zeb1 was involved in the development of CRC. m6A-induced lncRNA RP11 can trigger the dissemination of CRC cells via post-translational upregulation of Zeb1. Considering the high and specific levels of RP11 in CRC tissues, our present study paves the way for further investigations of RP11 as a predictive biomarker or therapeutic target for CRC.
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CRC
Zeb1
m6A
hnRNPA2B1
Cell dissemination
Cancer Research
Oncology
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name:Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, and Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong, China
type:PostalAddress
type:Organization
name:Panpan An
affiliation:
name:Sun Yat-sen University, Guangzhou
address:
name:Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, and Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong, China
type:PostalAddress
type:Organization
name:Linlin Lu
affiliation:
name:Sun Yat-sen University, Guangzhou
address:
name:Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, and Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong, China
type:PostalAddress
type:Organization
name:Nan Luo
affiliation:
name:Sun Yat-sen University, Guangzhou
address:
name:Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, and Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong, China
type:PostalAddress
type:Organization
name:Jun Du
affiliation:
name:Sun Yat-sen University, Guangzhou
address:
name:Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, and Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong, China
type:PostalAddress
type:Organization
name:Hong Shan
affiliation:
name:The Fifth Affiliated Hospital of Sun Yat-sen University
address:
name:Key Laboratory of Biomedical Imaging of Guangdong Province, Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China
type:PostalAddress
type:Organization
name:Huanliang Liu
affiliation:
name:Sun Yat-sen University, Guangzhou
address:
name:Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
type:PostalAddress
type:Organization
name:Sun Yat-sen University
address:
name:Department of Clinical Laboratory, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
type:PostalAddress
type:Organization
email:[email protected]
name:Hongsheng Wang
url:http://orcid.org/0000-0002-0054-4820
affiliation:
name:Sun Yat-sen University, Guangzhou
address:
name:Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, and Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong, China
type:PostalAddress
type:Organization
email:[email protected]
PostalAddress:
name:Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, and Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong, China
name:Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
name:Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
name:Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
name:Department of Pharmacy, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China
name:Department of Clinical Laboratory, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China
name:Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, and Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong, China
name:Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, and Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong, China
name:Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, and Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong, China
name:Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, and Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong, China
name:Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, and Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong, China
name:Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, and Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong, China
name:Key Laboratory of Biomedical Imaging of Guangdong Province, Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China
name:Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
name:Department of Clinical Laboratory, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
name:Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, and Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong, China
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