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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

Long noncoding RNAs (lncRNAs) expression in esophageal squamous cell carcinoma (ESCC). (a) Three differentially expressed lncRNAs, HOTAIR, ESCCAL-1, and ESCCAL-5, from microarray detection. The average intensity of expression in normal tissues (N) and tumors (T) is plotted with their standard deviations. (b) Validation of HOTAIR, ESCCAL-1, and ESCCAL-5 with independent patient samples by PCR analysis. The amplicons were separated with 2% agarose gel. GAPDH was used as an internal control. Significance is *P < 0.05, **P < 0.01.
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fig2: Long noncoding RNAs (lncRNAs) expression in esophageal squamous cell carcinoma (ESCC). (a) Three differentially expressed lncRNAs, HOTAIR, ESCCAL-1, and ESCCAL-5, from microarray detection. The average intensity of expression in normal tissues (N) and tumors (T) is plotted with their standard deviations. (b) Validation of HOTAIR, ESCCAL-1, and ESCCAL-5 with independent patient samples by PCR analysis. The amplicons were separated with 2% agarose gel. GAPDH was used as an internal control. Significance is *P < 0.05, **P < 0.01.

Mentions: LncRNAs are emerging as a novel class of noncoding RNAs that are pervasively transcribed in the genome, but there is limited functional knowledge about them. High-throughput screening of lncRNAs from ESCC has been poorly studied, except for a recent report of overexpressed lncRNA, AFAP1-AS1, in esophageal adenocarcinoma [21]. In our study, a total of 7,419 intergenic lncRNAs and other transcripts of uncertain coding potential were examined, and we identified 410 DE-lncRNAs in ESCC relative to adjacent normal esophageal tissues. We named the anonymous lncRNAs ESCC Associated Long noncoding RNAs (ESCCAL, Supplementary Table S1). Expression of HOTAIR lncRNA is increased in various cancers [14–17, 26], and it is also significantly increased in our analysis of ESCC (Figure 2(a)). In addition, we confirmed another two upregulated lncRNAs that are differentially expressed in ESCC and that we have named ESCCAL-1, and ESCCAL-5. The increased and differential expression of HOTAIR, ESCCAL-1 and ESCCAL-5 in ESCC tissue relative to adjacent nonneoplastic tissue was independently assessed with PCR methods in matched-pair tissue samples from three additional ESCC patients and the results are consistent with the microarray analysis (Figure 2(b)). Interestingly, except for HOTAIR, other previously reported lncRNAs (i.e., MALAT-1, PCAT-1 and AFAP1-AS1) are not differentially expressed in our analysis of ESCC. Therefore, the DE-lncRNAs that we have identified may be a unique property of ESCC, and we are currently using a population-based analysis to characterize these DE-lncRNAs as potential genomic biomarkers and regulatory elements in the dynamic process leading to ESCC.


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)

Long noncoding RNAs (lncRNAs) expression in esophageal squamous cell carcinoma (ESCC). (a) Three differentially expressed lncRNAs, HOTAIR, ESCCAL-1, and ESCCAL-5, from microarray detection. The average intensity of expression in normal tissues (N) and tumors (T) is plotted with their standard deviations. (b) Validation of HOTAIR, ESCCAL-1, and ESCCAL-5 with independent patient samples by PCR analysis. The amplicons were separated with 2% agarose gel. GAPDH was used as an internal control. Significance is *P < 0.05, **P < 0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3814080&req=5

fig2: Long noncoding RNAs (lncRNAs) expression in esophageal squamous cell carcinoma (ESCC). (a) Three differentially expressed lncRNAs, HOTAIR, ESCCAL-1, and ESCCAL-5, from microarray detection. The average intensity of expression in normal tissues (N) and tumors (T) is plotted with their standard deviations. (b) Validation of HOTAIR, ESCCAL-1, and ESCCAL-5 with independent patient samples by PCR analysis. The amplicons were separated with 2% agarose gel. GAPDH was used as an internal control. Significance is *P < 0.05, **P < 0.01.
Mentions: LncRNAs are emerging as a novel class of noncoding RNAs that are pervasively transcribed in the genome, but there is limited functional knowledge about them. High-throughput screening of lncRNAs from ESCC has been poorly studied, except for a recent report of overexpressed lncRNA, AFAP1-AS1, in esophageal adenocarcinoma [21]. In our study, a total of 7,419 intergenic lncRNAs and other transcripts of uncertain coding potential were examined, and we identified 410 DE-lncRNAs in ESCC relative to adjacent normal esophageal tissues. We named the anonymous lncRNAs ESCC Associated Long noncoding RNAs (ESCCAL, Supplementary Table S1). Expression of HOTAIR lncRNA is increased in various cancers [14–17, 26], and it is also significantly increased in our analysis of ESCC (Figure 2(a)). In addition, we confirmed another two upregulated lncRNAs that are differentially expressed in ESCC and that we have named ESCCAL-1, and ESCCAL-5. The increased and differential expression of HOTAIR, ESCCAL-1 and ESCCAL-5 in ESCC tissue relative to adjacent nonneoplastic tissue was independently assessed with PCR methods in matched-pair tissue samples from three additional ESCC patients and the results are consistent with the microarray analysis (Figure 2(b)). Interestingly, except for HOTAIR, other previously reported lncRNAs (i.e., MALAT-1, PCAT-1 and AFAP1-AS1) are not differentially expressed in our analysis of ESCC. Therefore, the DE-lncRNAs that we have identified may be a unique property of ESCC, and we are currently using a population-based analysis to characterize these DE-lncRNAs as potential genomic biomarkers and regulatory elements in the dynamic process leading to ESCC.

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