Long noncoding intronic RNAs are differentially expressed in primary and metastatic pancreatic cancer
<p>Abstract</p> <p>Background</p> <p>Pancreatic ductal adenocarcinoma (PDAC) is known by its aggressiveness and lack of effective therapeutic options. Thus, improvement in current knowledge of molecular changes associated with pancreatic cancer is urgently needed to exp...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2011-11-01
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| Series: | Molecular Cancer |
| Subjects: | |
| Online Access: | http://www.molecular-cancer.com/content/10/1/141 |
| _version_ | 1818065595744124928 |
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| author | Tahira Ana C Kubrusly Márcia S Faria Michele F Dazzani Bianca Fonseca Rogério S Maracaja-Coutinho Vinicius Verjovski-Almeida Sergio Machado Marcel CC Reis Eduardo M |
| author_facet | Tahira Ana C Kubrusly Márcia S Faria Michele F Dazzani Bianca Fonseca Rogério S Maracaja-Coutinho Vinicius Verjovski-Almeida Sergio Machado Marcel CC Reis Eduardo M |
| author_sort | Tahira Ana C |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Pancreatic ductal adenocarcinoma (PDAC) is known by its aggressiveness and lack of effective therapeutic options. Thus, improvement in current knowledge of molecular changes associated with pancreatic cancer is urgently needed to explore novel venues of diagnostics and treatment of this dismal disease. While there is mounting evidence that long noncoding RNAs (lncRNAs) transcribed from intronic and intergenic regions of the human genome may play different roles in the regulation of gene expression in normal and cancer cells, their expression pattern and biological relevance in pancreatic cancer is currently unknown. In the present work we investigated the relative abundance of a collection of lncRNAs in patients' pancreatic tissue samples aiming at identifying gene expression profiles correlated to pancreatic cancer and metastasis.</p> <p>Methods</p> <p>Custom 3,355-element spotted cDNA microarray interrogating protein-coding genes and putative lncRNA were used to obtain expression profiles from 38 clinical samples of tumor and non-tumor pancreatic tissues. Bioinformatics analyses were performed to characterize structure and conservation of lncRNAs expressed in pancreatic tissues, as well as to identify expression signatures correlated to tissue histology. Strand-specific reverse transcription followed by PCR and qRT-PCR were employed to determine strandedness of lncRNAs and to validate microarray results, respectively.</p> <p>Results</p> <p>We show that subsets of intronic/intergenic lncRNAs are expressed across tumor and non-tumor pancreatic tissue samples. Enrichment of promoter-associated chromatin marks and over-representation of conserved DNA elements and stable secondary structure predictions suggest that these transcripts are generated from independent transcriptional units and that at least a fraction is under evolutionary selection, and thus potentially functional.</p> <p>Statistically significant expression signatures comprising protein-coding mRNAs and lncRNAs that correlate to PDAC or to pancreatic cancer metastasis were identified. Interestingly, <it>loci </it>harboring intronic lncRNAs differentially expressed in PDAC metastases were enriched in genes associated to the MAPK pathway. Orientation-specific RT-PCR documented that intronic transcripts are expressed in sense, antisense or both orientations relative to protein-coding mRNAs. Differential expression of a subset of intronic lncRNAs (<it>PPP3CB</it>, <it>MAP3K14 </it>and <it>DAPK1 loci</it>) in metastatic samples was confirmed by Real-Time PCR.</p> <p>Conclusion</p> <p>Our findings reveal sets of intronic lncRNAs expressed in pancreatic tissues whose abundance is correlated to PDAC or metastasis, thus pointing to the potential relevance of this class of transcripts in biological processes related to malignant transformation and metastasis in pancreatic cancer.</p> |
| first_indexed | 2024-12-10T14:54:24Z |
| format | Article |
| id | doaj.art-4a71d27b5af649cc96145ace6828723b |
| institution | Directory Open Access Journal |
| issn | 1476-4598 |
| language | English |
| last_indexed | 2024-12-10T14:54:24Z |
| publishDate | 2011-11-01 |
| publisher | BMC |
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| series | Molecular Cancer |
| spelling | doaj.art-4a71d27b5af649cc96145ace6828723b2022-12-22T01:44:20ZengBMCMolecular Cancer1476-45982011-11-0110114110.1186/1476-4598-10-141Long noncoding intronic RNAs are differentially expressed in primary and metastatic pancreatic cancerTahira Ana CKubrusly Márcia SFaria Michele FDazzani BiancaFonseca Rogério SMaracaja-Coutinho ViniciusVerjovski-Almeida SergioMachado Marcel CCReis Eduardo M<p>Abstract</p> <p>Background</p> <p>Pancreatic ductal adenocarcinoma (PDAC) is known by its aggressiveness and lack of effective therapeutic options. Thus, improvement in current knowledge of molecular changes associated with pancreatic cancer is urgently needed to explore novel venues of diagnostics and treatment of this dismal disease. While there is mounting evidence that long noncoding RNAs (lncRNAs) transcribed from intronic and intergenic regions of the human genome may play different roles in the regulation of gene expression in normal and cancer cells, their expression pattern and biological relevance in pancreatic cancer is currently unknown. In the present work we investigated the relative abundance of a collection of lncRNAs in patients' pancreatic tissue samples aiming at identifying gene expression profiles correlated to pancreatic cancer and metastasis.</p> <p>Methods</p> <p>Custom 3,355-element spotted cDNA microarray interrogating protein-coding genes and putative lncRNA were used to obtain expression profiles from 38 clinical samples of tumor and non-tumor pancreatic tissues. Bioinformatics analyses were performed to characterize structure and conservation of lncRNAs expressed in pancreatic tissues, as well as to identify expression signatures correlated to tissue histology. Strand-specific reverse transcription followed by PCR and qRT-PCR were employed to determine strandedness of lncRNAs and to validate microarray results, respectively.</p> <p>Results</p> <p>We show that subsets of intronic/intergenic lncRNAs are expressed across tumor and non-tumor pancreatic tissue samples. Enrichment of promoter-associated chromatin marks and over-representation of conserved DNA elements and stable secondary structure predictions suggest that these transcripts are generated from independent transcriptional units and that at least a fraction is under evolutionary selection, and thus potentially functional.</p> <p>Statistically significant expression signatures comprising protein-coding mRNAs and lncRNAs that correlate to PDAC or to pancreatic cancer metastasis were identified. Interestingly, <it>loci </it>harboring intronic lncRNAs differentially expressed in PDAC metastases were enriched in genes associated to the MAPK pathway. Orientation-specific RT-PCR documented that intronic transcripts are expressed in sense, antisense or both orientations relative to protein-coding mRNAs. Differential expression of a subset of intronic lncRNAs (<it>PPP3CB</it>, <it>MAP3K14 </it>and <it>DAPK1 loci</it>) in metastatic samples was confirmed by Real-Time PCR.</p> <p>Conclusion</p> <p>Our findings reveal sets of intronic lncRNAs expressed in pancreatic tissues whose abundance is correlated to PDAC or metastasis, thus pointing to the potential relevance of this class of transcripts in biological processes related to malignant transformation and metastasis in pancreatic cancer.</p>http://www.molecular-cancer.com/content/10/1/141pancreatic cancermolecular markersnoncoding RNAsintronic transcriptionmetastasis<it>MAPK </it>pathwaycDNA microarrays |
| spellingShingle | Tahira Ana C Kubrusly Márcia S Faria Michele F Dazzani Bianca Fonseca Rogério S Maracaja-Coutinho Vinicius Verjovski-Almeida Sergio Machado Marcel CC Reis Eduardo M Long noncoding intronic RNAs are differentially expressed in primary and metastatic pancreatic cancer Molecular Cancer pancreatic cancer molecular markers noncoding RNAs intronic transcription metastasis <it>MAPK </it> pathway cDNA microarrays |
| title | Long noncoding intronic RNAs are differentially expressed in primary and metastatic pancreatic cancer |
| title_full | Long noncoding intronic RNAs are differentially expressed in primary and metastatic pancreatic cancer |
| title_fullStr | Long noncoding intronic RNAs are differentially expressed in primary and metastatic pancreatic cancer |
| title_full_unstemmed | Long noncoding intronic RNAs are differentially expressed in primary and metastatic pancreatic cancer |
| title_short | Long noncoding intronic RNAs are differentially expressed in primary and metastatic pancreatic cancer |
| title_sort | long noncoding intronic rnas are differentially expressed in primary and metastatic pancreatic cancer |
| topic | pancreatic cancer molecular markers noncoding RNAs intronic transcription metastasis <it>MAPK </it> pathway cDNA microarrays |
| url | http://www.molecular-cancer.com/content/10/1/141 |
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