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Integrated analysis of DNA methylation and microRNA regulation of the lung adenocarcinoma transcriptome.

Du J, Zhang L - Oncol. Rep. (2015)

Bottom Line: DEGs were centrally modified by histones of tri-methylation of lysine 27 on histone H3 (H3K27me3) and di-acetylation of lysine 12 or 20 on histone H2 (H2BK12/20AC).Upstream TFs of DEGs were enriched in different ChIP-seq clusters, such as glucocorticoid receptors (GRs).Two miRNAs (miR-126-3p and miR-30c-2-3p) and three TFs including homeobox A5 (HOXA5), Meis homeobox 1 (MEIS1) and T-box 5 (TBX5), played important roles in the integrated regulatory network conjointly.

View Article: PubMed Central - PubMed

Affiliation: Department of Thoracic Surgery, Chinese Medical University Affiliated No. 1 Hospital, Shenyang, Liaoning 110001, P.R. China.

ABSTRACT
Lung adenocarcinoma, as a common type of non-small cell lung cancer (40%), poses a significant threat to public health worldwide. The present study aimed to determine the transcriptional regulatory mechanisms in lung adenocarcinoma. Illumina sequence data GSE 37764 including expression profiling, methylation profiling and non-coding RNA profiling of 6 never-smoker Korean female patients with non-small cell lung adenocarcinoma were obtained from the Gene Expression Omnibus (GEO) database. Differentially methylated genes, differentially expressed genes (DEGs) and differentially expressed microRNAs (miRNAs) between normal and tumor tissues of the same patients were screened with tools in R. Functional enrichment analysis of a variety of differential genes was performed. DEG-specific methylation and transcription factors (TFs) were analyzed with ENCODE ChIP-seq. The integrated regulatory network of DEGs, TFs and miRNAs was constructed. Several overlapping DEGs, such as v-ets avian erythroblastosis virus E26 oncogene homolog (ERG) were screened. DEGs were centrally modified by histones of tri-methylation of lysine 27 on histone H3 (H3K27me3) and di-acetylation of lysine 12 or 20 on histone H2 (H2BK12/20AC). Upstream TFs of DEGs were enriched in different ChIP-seq clusters, such as glucocorticoid receptors (GRs). Two miRNAs (miR-126-3p and miR-30c-2-3p) and three TFs including homeobox A5 (HOXA5), Meis homeobox 1 (MEIS1) and T-box 5 (TBX5), played important roles in the integrated regulatory network conjointly. These DEGs, and DEG-related histone modifications, TFs and miRNAs may be important in the pathogenesis of lung adenocarcinoma. The present results may indicate directions for the next step in the study of the further elucidation and targeted prevention of lung adenocarcinoma.

No MeSH data available.


Related in: MedlinePlus

Transcription factor-microRNA regulatory network of the differentially expressed genes. Differentially expressed genes, transcript factors and differentially expressed miRNAs are shown in yellow, green and blue, respectively.
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f7-or-34-02-0585: Transcription factor-microRNA regulatory network of the differentially expressed genes. Differentially expressed genes, transcript factors and differentially expressed miRNAs are shown in yellow, green and blue, respectively.

Mentions: DEGs were regulated by TFs and miRNAs, and the regulatory network was constructed as shown in Fig. 7. There were 116 DEGs, 72 TFs and 7 differentially expressed miRNAs. miR-126-3p served as a ‘hub’ in the gene regulatory network which regulated 26 DEGs. The TF MEIS1 was another ‘hub’, which also regulated 22 DEGs and miR-30c-2-3p. Several sub-networks with homeobox A5 (HOXA5), Meis homeobox 1 (MEIS1), T-box 5 (TBX5), miR-126-3p and miR-30c-2-3p as centers shared several nodes and then formed another greater regulatory network. The remaining sub-networks were detached from each other.


Integrated analysis of DNA methylation and microRNA regulation of the lung adenocarcinoma transcriptome.

Du J, Zhang L - Oncol. Rep. (2015)

Transcription factor-microRNA regulatory network of the differentially expressed genes. Differentially expressed genes, transcript factors and differentially expressed miRNAs are shown in yellow, green and blue, respectively.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4487669&req=5

f7-or-34-02-0585: Transcription factor-microRNA regulatory network of the differentially expressed genes. Differentially expressed genes, transcript factors and differentially expressed miRNAs are shown in yellow, green and blue, respectively.
Mentions: DEGs were regulated by TFs and miRNAs, and the regulatory network was constructed as shown in Fig. 7. There were 116 DEGs, 72 TFs and 7 differentially expressed miRNAs. miR-126-3p served as a ‘hub’ in the gene regulatory network which regulated 26 DEGs. The TF MEIS1 was another ‘hub’, which also regulated 22 DEGs and miR-30c-2-3p. Several sub-networks with homeobox A5 (HOXA5), Meis homeobox 1 (MEIS1), T-box 5 (TBX5), miR-126-3p and miR-30c-2-3p as centers shared several nodes and then formed another greater regulatory network. The remaining sub-networks were detached from each other.

Bottom Line: DEGs were centrally modified by histones of tri-methylation of lysine 27 on histone H3 (H3K27me3) and di-acetylation of lysine 12 or 20 on histone H2 (H2BK12/20AC).Upstream TFs of DEGs were enriched in different ChIP-seq clusters, such as glucocorticoid receptors (GRs).Two miRNAs (miR-126-3p and miR-30c-2-3p) and three TFs including homeobox A5 (HOXA5), Meis homeobox 1 (MEIS1) and T-box 5 (TBX5), played important roles in the integrated regulatory network conjointly.

View Article: PubMed Central - PubMed

Affiliation: Department of Thoracic Surgery, Chinese Medical University Affiliated No. 1 Hospital, Shenyang, Liaoning 110001, P.R. China.

ABSTRACT
Lung adenocarcinoma, as a common type of non-small cell lung cancer (40%), poses a significant threat to public health worldwide. The present study aimed to determine the transcriptional regulatory mechanisms in lung adenocarcinoma. Illumina sequence data GSE 37764 including expression profiling, methylation profiling and non-coding RNA profiling of 6 never-smoker Korean female patients with non-small cell lung adenocarcinoma were obtained from the Gene Expression Omnibus (GEO) database. Differentially methylated genes, differentially expressed genes (DEGs) and differentially expressed microRNAs (miRNAs) between normal and tumor tissues of the same patients were screened with tools in R. Functional enrichment analysis of a variety of differential genes was performed. DEG-specific methylation and transcription factors (TFs) were analyzed with ENCODE ChIP-seq. The integrated regulatory network of DEGs, TFs and miRNAs was constructed. Several overlapping DEGs, such as v-ets avian erythroblastosis virus E26 oncogene homolog (ERG) were screened. DEGs were centrally modified by histones of tri-methylation of lysine 27 on histone H3 (H3K27me3) and di-acetylation of lysine 12 or 20 on histone H2 (H2BK12/20AC). Upstream TFs of DEGs were enriched in different ChIP-seq clusters, such as glucocorticoid receptors (GRs). Two miRNAs (miR-126-3p and miR-30c-2-3p) and three TFs including homeobox A5 (HOXA5), Meis homeobox 1 (MEIS1) and T-box 5 (TBX5), played important roles in the integrated regulatory network conjointly. These DEGs, and DEG-related histone modifications, TFs and miRNAs may be important in the pathogenesis of lung adenocarcinoma. The present results may indicate directions for the next step in the study of the further elucidation and targeted prevention of lung adenocarcinoma.

No MeSH data available.


Related in: MedlinePlus