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Title:
KIAA1429 contributes to liver cancer progression through N6-methyladenosine-dependent post-transcriptional modification of GATA3 | Molecular Cancer
Description:
Background N6-methyladenosine (m6A) modification, the most abundant internal methylation of eukaryotic RNA transcripts, is critically implicated in RNA processing. As the largest known component in the m6A methyltransferase complex, KIAA1429 plays a vital role in m6A methylation. However, its function and mechanism in hepatocellular carcinoma (HCC) remain poorly defined. Methods Quantitative PCR, western blot and immunohistochemistry were used to measure the expression of KIAA1429 in HCC. The effects of KIAA1429 on the malignant phenotypes of hepatoma cells were examined in vitro and in vivo. MeRIP-seq, RIP-seq and RNA-seq were performed to identify the target genes of KIAA1429. Results KIAA1429 was considerably upregulated in HCC tissues. High expression of KIAA1429 was associated with poor prognosis among HCC patients. Silencing KIAA1429 suppressed cell proliferation and metastasis in vitro and in vivo. GATA3 was identified as the direct downstream target of KIAA1429-mediated m6A modification. KIAA1429 induced m6A methylation on the 3′ UTR of GATA3 pre-mRNA, leading to the separation of the RNA-binding protein HuR and the degradation of GATA3 pre-mRNA. Strikingly, a long noncoding RNA (lncRNA) GATA3-AS, transcribed from the antisense strand of the GATA3 gene, functioned as a cis-acting element for the preferential interaction of KIAA1429 with GATA3 pre-mRNA. Accordingly, we found that the tumor growth and metastasis driven by KIAA1429 or GATA3-AS were mediated by GATA3. Conclusion Our study proposed a complex KIAA1429-GATA3 regulatory model based on m6A modification and provided insights into the epi-transcriptomic dysregulation in hepatocarcinogenesis and metastasis.
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Keywords {🔍}
kiaa, gata, cells, expression, premrna, pubmed, additional, rna, file, gataas, skhep, hcclm, article, cell, control, analysis, hcc, google, scholar, mrna, cas, data, sirnas, cancer, modification, hur, mettl, figures, methylation, fig, transfected, tissues, metastasis, central, utr, knockdown, luciferase, qpcr, figs, assays, protein, gene, relative, significantly, china, presented, bars, patients, tumor, scale,
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n6-methyladenosine-dependent post-transcriptional modification mir-133a-3p/high mobility group targeting mir-199a/b-5p sex-determining gene sex-lethal m6a-ythdf2-dependent manner [11] n6-methyladenosine-independent manner luciferase reporter pmirglo-gata3-wt pmirglo-gata3-wt luciferase reporter ythdf2-dependent posttranscriptional silencing pmirglo-gata3-mut luciferase reporter m6a-modified gata3 pre-mrna article download pdf accelerating pri-mir221/222 maturation histone h3 served post-transcriptional level rna n6-methyladenosine methyltransferase 125 bp paired-end reads paired-end clean reads qubit®rna assay kit washed rna-protein complexes n6-methyladenosine merip-seq splicing-specific chromatin signature pivotal cancer-promoting events a-igf2bp2-dependent mechanism kiaa429-mediated m6a modification locked nucleic acid-fluorescence m6a-dependent manner hypoxia/reoxygenation-treated cardiomyocytes regulating microrna-29b expression m6a epi-transcriptomic modification hepatocellular carcinoma pmirglo-gata3-wt showed epi-transcriptomic regulation underlying human genome grch37/hg19 anti-n6-methyladenosine wound-healing migration assays kiaa1429-mediated m6a methylation pmirglo-gata3-mut showed gata3 pre-mrna sustained m-mulv reverse transcriptase impairs gls-mediated metabolism kiaa1429-mediated m6a modification arraystar seq-star™ poly dynamic rna modifications numerous tumor-suppressive genes tail intravenous injection rna-binding protein hur endogenous anti-kiaa1429 antibody article lan molecular mechanism underlying
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headline:KIAA1429 contributes to liver cancer progression through N6-methyladenosine-dependent post-transcriptional modification of GATA3
description:N6-methyladenosine (m6A) modification, the most abundant internal methylation of eukaryotic RNA transcripts, is critically implicated in RNA processing. As the largest known component in the m6A methyltransferase complex, KIAA1429 plays a vital role in m6A methylation. However, its function and mechanism in hepatocellular carcinoma (HCC) remain poorly defined. Quantitative PCR, western blot and immunohistochemistry were used to measure the expression of KIAA1429 in HCC. The effects of KIAA1429 on the malignant phenotypes of hepatoma cells were examined in vitro and in vivo. MeRIP-seq, RIP-seq and RNA-seq were performed to identify the target genes of KIAA1429. KIAA1429 was considerably upregulated in HCC tissues. High expression of KIAA1429 was associated with poor prognosis among HCC patients. Silencing KIAA1429 suppressed cell proliferation and metastasis in vitro and in vivo. GATA3 was identified as the direct downstream target of KIAA1429-mediated m6A modification. KIAA1429 induced m6A methylation on the 3′ UTR of GATA3 pre-mRNA, leading to the separation of the RNA-binding protein HuR and the degradation of GATA3 pre-mRNA. Strikingly, a long noncoding RNA (lncRNA) GATA3-AS, transcribed from the antisense strand of the GATA3 gene, functioned as a cis-acting element for the preferential interaction of KIAA1429 with GATA3 pre-mRNA. Accordingly, we found that the tumor growth and metastasis driven by KIAA1429 or GATA3-AS were mediated by GATA3. Our study proposed a complex KIAA1429-GATA3 regulatory model based on m6A modification and provided insights into the epi-transcriptomic dysregulation in hepatocarcinogenesis and metastasis.
datePublished:2019-12-19T00:00:00Z
dateModified:2019-12-19T00:00:00Z
pageStart:1
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keywords:
Hepatocellular carcinoma
N6-methyladenosine
KIAA1429
GATA3
GATA3-AS
Cancer Research
Oncology
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headline:KIAA1429 contributes to liver cancer progression through N6-methyladenosine-dependent post-transcriptional modification of GATA3
description:N6-methyladenosine (m6A) modification, the most abundant internal methylation of eukaryotic RNA transcripts, is critically implicated in RNA processing. As the largest known component in the m6A methyltransferase complex, KIAA1429 plays a vital role in m6A methylation. However, its function and mechanism in hepatocellular carcinoma (HCC) remain poorly defined. Quantitative PCR, western blot and immunohistochemistry were used to measure the expression of KIAA1429 in HCC. The effects of KIAA1429 on the malignant phenotypes of hepatoma cells were examined in vitro and in vivo. MeRIP-seq, RIP-seq and RNA-seq were performed to identify the target genes of KIAA1429. KIAA1429 was considerably upregulated in HCC tissues. High expression of KIAA1429 was associated with poor prognosis among HCC patients. Silencing KIAA1429 suppressed cell proliferation and metastasis in vitro and in vivo. GATA3 was identified as the direct downstream target of KIAA1429-mediated m6A modification. KIAA1429 induced m6A methylation on the 3′ UTR of GATA3 pre-mRNA, leading to the separation of the RNA-binding protein HuR and the degradation of GATA3 pre-mRNA. Strikingly, a long noncoding RNA (lncRNA) GATA3-AS, transcribed from the antisense strand of the GATA3 gene, functioned as a cis-acting element for the preferential interaction of KIAA1429 with GATA3 pre-mRNA. Accordingly, we found that the tumor growth and metastasis driven by KIAA1429 or GATA3-AS were mediated by GATA3. Our study proposed a complex KIAA1429-GATA3 regulatory model based on m6A modification and provided insights into the epi-transcriptomic dysregulation in hepatocarcinogenesis and metastasis.
datePublished:2019-12-19T00:00:00Z
dateModified:2019-12-19T00:00:00Z
pageStart:1
pageEnd:19
license:http://creativecommons.org/publicdomain/zero/1.0/
sameAs:https://doi.org/10.1186/s12943-019-1106-z
keywords:
Hepatocellular carcinoma
N6-methyladenosine
KIAA1429
GATA3
GATA3-AS
Cancer Research
Oncology
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name:Department of Hepatobiliary Surgery, Guizhou Provincial People’s Hospital, Guiyang, China
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