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Integrated analysis of long noncoding RNA and coding RNA expression in esophageal squamous cell carcinoma.

Cao W, Wu W, Shi F, Chen X, Wu L, Yang K, Tian F, Zhu M, Chen G, Wang W, Biddle FG, Gu J - Int J Genomics (2013)

Bottom Line: We identified differentially expressed lncRNAs and coding RNAs in ESCC relative to their matched normal tissue counterparts and validated the result using polymerase chain reaction analysis.Furthermore, we identified differentially expressed lncRNAs that are co-located and co-expressed with differentially expressed coding RNAs in ESCC and the results point to a potential interaction between lncRNAs and neighboring coding genes that affect ether lipid metabolism, and the interaction may contribute to the development of ESCC.These data provide compelling evidence for a potential novel genomic biomarker of esophageal squamous cell cancer.

View Article: PubMed Central - PubMed

Affiliation: Clinical Research Center, People's Hospital of Zhengzhou, 33 Yellow River Road, Zhengzhou, Henan 45003, China.

ABSTRACT
Tumorigenesis is a complex dynamic biological process that includes multiple steps of genetic and epigenetic alterations, aberrant expression of noncoding RNA, and changes in the expression profiles of coding genes. We call the collection of those perturbations in genome space the "cancer initiatome." Long noncoding RNAs (lncRNAs) are pervasively transcribed in the genome and they have key regulatory functions in chromatin remodeling and gene expression. Spatiotemporal variation in the expression of lncRNAs has been observed in development and disease states, including cancer. A few dysregulated lncRNAs have been studied in cancers, but the role of lncRNAs in the cancer initiatome remains largely unknown, especially in esophageal squamous cell carcinoma (ESCC). We conducted a genome-wide screen of the expression of lncRNAs and coding RNAs from ESCC and matched adjacent nonneoplastic normal tissues. We identified differentially expressed lncRNAs and coding RNAs in ESCC relative to their matched normal tissue counterparts and validated the result using polymerase chain reaction analysis. Furthermore, we identified differentially expressed lncRNAs that are co-located and co-expressed with differentially expressed coding RNAs in ESCC and the results point to a potential interaction between lncRNAs and neighboring coding genes that affect ether lipid metabolism, and the interaction may contribute to the development of ESCC. These data provide compelling evidence for a potential novel genomic biomarker of esophageal squamous cell cancer.

No MeSH data available.


Related in: MedlinePlus

Identification of lncRNAs co-located and co-expressed neighboring genes in esophageal squamous cell carcinoma (ESCC). (a) Identification of neighboring genes of the DE-lncRNAs. The genomic coordinate information of 410 DE-lncRNAs was used to search neighboring genes whose genomic locations are within ~5 kb upstream and ~1 kb downstream of the lncRNA and may extend to 1000 kb in both directions using GREAT software (http://bejerano.stanford.edu/great/public/html/index.php). The percentage of DE-lncRNAs harboring zero, one, or two neighboring genes is presented. (b) Gene Ontology (GO) enrichment analysis of lncRNAs co-located genes. Identified gene enriched pathways/terms are listed on the left; the length of horizontal bars and the numbers on the right indicate the percentage of genes involved in each pathway/term. (c) LncRNAs co-located and co-expressed coding mRNAs. Overlap of 538 DE-lncRNA co-located genes with 3307 DE-mRNAs in microarrays identified 76 lncRNAs co-located and co-expressed coding mRNAs (list in Table 2). GO enrichment analysis suggests phospholipase D1 (PLD1) and lysophosphatidylcholine acyltransferase1 (LPCAT1) are involved in ether lipid metabolism pathway. Genomic location shows that PLD1 is located at −22,068 bp upstream of ESCCAL-337 lncRNA on Chr 3 and LPCAT1 is at −21,250 bp upstream of ESCCAL-356 lncRNA on Chr 5.
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fig3: Identification of lncRNAs co-located and co-expressed neighboring genes in esophageal squamous cell carcinoma (ESCC). (a) Identification of neighboring genes of the DE-lncRNAs. The genomic coordinate information of 410 DE-lncRNAs was used to search neighboring genes whose genomic locations are within ~5 kb upstream and ~1 kb downstream of the lncRNA and may extend to 1000 kb in both directions using GREAT software (http://bejerano.stanford.edu/great/public/html/index.php). The percentage of DE-lncRNAs harboring zero, one, or two neighboring genes is presented. (b) Gene Ontology (GO) enrichment analysis of lncRNAs co-located genes. Identified gene enriched pathways/terms are listed on the left; the length of horizontal bars and the numbers on the right indicate the percentage of genes involved in each pathway/term. (c) LncRNAs co-located and co-expressed coding mRNAs. Overlap of 538 DE-lncRNA co-located genes with 3307 DE-mRNAs in microarrays identified 76 lncRNAs co-located and co-expressed coding mRNAs (list in Table 2). GO enrichment analysis suggests phospholipase D1 (PLD1) and lysophosphatidylcholine acyltransferase1 (LPCAT1) are involved in ether lipid metabolism pathway. Genomic location shows that PLD1 is located at −22,068 bp upstream of ESCCAL-337 lncRNA on Chr 3 and LPCAT1 is at −21,250 bp upstream of ESCCAL-356 lncRNA on Chr 5.

Mentions: LncRNAs have been reported to coordinate the regulation of neighboring coding genes through a “locus control” process [11]. We wondered whether such a “locus control” process could operate in ESCC development, and, therefore, we searched neighboring genes of the 410 DE-lncRNAs in the genome. The majority (98.8%) of the 410 DE-lncRNAs harbor neighboring coding genes whose genomic locations are within ~5 kb upstream and ~1 kb downstream of the lncRNA and may extend to 1000 kb in both directions (Figure 3(a)). Interrogation of 538 coding genes that are neighbors of these DE-lncRNAs (DE-lncRNAs co-located genes) revealed predicted functions in 9 common pathways such as the AP1 transcription factor network, integrin-linked kinase signaling, several signaling pathways in adherens junctions, and FOXO family signaling (Figure 3(b)).


Integrated analysis of long noncoding RNA and coding RNA expression in esophageal squamous cell carcinoma.

Cao W, Wu W, Shi F, Chen X, Wu L, Yang K, Tian F, Zhu M, Chen G, Wang W, Biddle FG, Gu J - Int J Genomics (2013)

Identification of lncRNAs co-located and co-expressed neighboring genes in esophageal squamous cell carcinoma (ESCC). (a) Identification of neighboring genes of the DE-lncRNAs. The genomic coordinate information of 410 DE-lncRNAs was used to search neighboring genes whose genomic locations are within ~5 kb upstream and ~1 kb downstream of the lncRNA and may extend to 1000 kb in both directions using GREAT software (http://bejerano.stanford.edu/great/public/html/index.php). The percentage of DE-lncRNAs harboring zero, one, or two neighboring genes is presented. (b) Gene Ontology (GO) enrichment analysis of lncRNAs co-located genes. Identified gene enriched pathways/terms are listed on the left; the length of horizontal bars and the numbers on the right indicate the percentage of genes involved in each pathway/term. (c) LncRNAs co-located and co-expressed coding mRNAs. Overlap of 538 DE-lncRNA co-located genes with 3307 DE-mRNAs in microarrays identified 76 lncRNAs co-located and co-expressed coding mRNAs (list in Table 2). GO enrichment analysis suggests phospholipase D1 (PLD1) and lysophosphatidylcholine acyltransferase1 (LPCAT1) are involved in ether lipid metabolism pathway. Genomic location shows that PLD1 is located at −22,068 bp upstream of ESCCAL-337 lncRNA on Chr 3 and LPCAT1 is at −21,250 bp upstream of ESCCAL-356 lncRNA on Chr 5.
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig3: Identification of lncRNAs co-located and co-expressed neighboring genes in esophageal squamous cell carcinoma (ESCC). (a) Identification of neighboring genes of the DE-lncRNAs. The genomic coordinate information of 410 DE-lncRNAs was used to search neighboring genes whose genomic locations are within ~5 kb upstream and ~1 kb downstream of the lncRNA and may extend to 1000 kb in both directions using GREAT software (http://bejerano.stanford.edu/great/public/html/index.php). The percentage of DE-lncRNAs harboring zero, one, or two neighboring genes is presented. (b) Gene Ontology (GO) enrichment analysis of lncRNAs co-located genes. Identified gene enriched pathways/terms are listed on the left; the length of horizontal bars and the numbers on the right indicate the percentage of genes involved in each pathway/term. (c) LncRNAs co-located and co-expressed coding mRNAs. Overlap of 538 DE-lncRNA co-located genes with 3307 DE-mRNAs in microarrays identified 76 lncRNAs co-located and co-expressed coding mRNAs (list in Table 2). GO enrichment analysis suggests phospholipase D1 (PLD1) and lysophosphatidylcholine acyltransferase1 (LPCAT1) are involved in ether lipid metabolism pathway. Genomic location shows that PLD1 is located at −22,068 bp upstream of ESCCAL-337 lncRNA on Chr 3 and LPCAT1 is at −21,250 bp upstream of ESCCAL-356 lncRNA on Chr 5.
Mentions: LncRNAs have been reported to coordinate the regulation of neighboring coding genes through a “locus control” process [11]. We wondered whether such a “locus control” process could operate in ESCC development, and, therefore, we searched neighboring genes of the 410 DE-lncRNAs in the genome. The majority (98.8%) of the 410 DE-lncRNAs harbor neighboring coding genes whose genomic locations are within ~5 kb upstream and ~1 kb downstream of the lncRNA and may extend to 1000 kb in both directions (Figure 3(a)). Interrogation of 538 coding genes that are neighbors of these DE-lncRNAs (DE-lncRNAs co-located genes) revealed predicted functions in 9 common pathways such as the AP1 transcription factor network, integrin-linked kinase signaling, several signaling pathways in adherens junctions, and FOXO family signaling (Figure 3(b)).

Bottom Line: We identified differentially expressed lncRNAs and coding RNAs in ESCC relative to their matched normal tissue counterparts and validated the result using polymerase chain reaction analysis.Furthermore, we identified differentially expressed lncRNAs that are co-located and co-expressed with differentially expressed coding RNAs in ESCC and the results point to a potential interaction between lncRNAs and neighboring coding genes that affect ether lipid metabolism, and the interaction may contribute to the development of ESCC.These data provide compelling evidence for a potential novel genomic biomarker of esophageal squamous cell cancer.

View Article: PubMed Central - PubMed

Affiliation: Clinical Research Center, People's Hospital of Zhengzhou, 33 Yellow River Road, Zhengzhou, Henan 45003, China.

ABSTRACT
Tumorigenesis is a complex dynamic biological process that includes multiple steps of genetic and epigenetic alterations, aberrant expression of noncoding RNA, and changes in the expression profiles of coding genes. We call the collection of those perturbations in genome space the "cancer initiatome." Long noncoding RNAs (lncRNAs) are pervasively transcribed in the genome and they have key regulatory functions in chromatin remodeling and gene expression. Spatiotemporal variation in the expression of lncRNAs has been observed in development and disease states, including cancer. A few dysregulated lncRNAs have been studied in cancers, but the role of lncRNAs in the cancer initiatome remains largely unknown, especially in esophageal squamous cell carcinoma (ESCC). We conducted a genome-wide screen of the expression of lncRNAs and coding RNAs from ESCC and matched adjacent nonneoplastic normal tissues. We identified differentially expressed lncRNAs and coding RNAs in ESCC relative to their matched normal tissue counterparts and validated the result using polymerase chain reaction analysis. Furthermore, we identified differentially expressed lncRNAs that are co-located and co-expressed with differentially expressed coding RNAs in ESCC and the results point to a potential interaction between lncRNAs and neighboring coding genes that affect ether lipid metabolism, and the interaction may contribute to the development of ESCC. These data provide compelling evidence for a potential novel genomic biomarker of esophageal squamous cell cancer.

No MeSH data available.


Related in: MedlinePlus