Global identification and characterization of lncRNAs that control inflammation in malignant cholangiocytes
Abstract Background Long noncoding RNAs (lncRNAs) are known to play important roles in different cell contexts, including cancers. However, little is known about lncRNAs in cholangiocarcinoma (CCA), a cholangiocyte malignancy with poor prognosis, and associated with chronic inflammation and damage t...
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| Format: | Article |
| Language: | English |
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BMC
2018-10-01
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| Series: | BMC Genomics |
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| Online Access: | http://link.springer.com/article/10.1186/s12864-018-5133-8 |
| _version_ | 1818505541612208128 |
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| author | Bo-Wei Han Hua Ye Pan-Pan Wei Bo He Cai Han Zhen-Hua Chen Yue-Qin Chen Wen-Tao Wang |
| author_facet | Bo-Wei Han Hua Ye Pan-Pan Wei Bo He Cai Han Zhen-Hua Chen Yue-Qin Chen Wen-Tao Wang |
| author_sort | Bo-Wei Han |
| collection | DOAJ |
| description | Abstract Background Long noncoding RNAs (lncRNAs) are known to play important roles in different cell contexts, including cancers. However, little is known about lncRNAs in cholangiocarcinoma (CCA), a cholangiocyte malignancy with poor prognosis, and associated with chronic inflammation and damage to the biliary epithelium. This study determined whether lncRNAs were dysregulated and participated in disease diagnosis or pivotal inflammation pathways through a genome-wide lncRNA screening and functional analysis. Results We firstly identified a large number of lncRNAs abnormally expressed between 9 pairs of cancerous and adjacent tissues of CCA, and between intra-hepatic CCA and extra-hepatic CCA through a genome-wide profiling. A set of aberrant differentially expressed lncRNAs were further validated in a training set (16 pairs) and a test set (11 pairs) of CCA patient samples. Following assessment of the diagnostic value of the 7 differentially expressed lncRNAs, we confirmed the optimal combination of H19, C3P1, AC005550.3, PVT1, and LPAL2 with area under the curve of 0.8828 [95% CI: 0.7441–1.021, P < 0.001], with 93.75% sensitivity and 81.25% specificity, at the cutoff point of − 0.2884 to distinguish the CCA tissue from the normal ones, suggesting that specific lncRNAs may have potential for detecting CCA. More importantly, the genome-wide locus and lncRNA/mRNA co-expression analyses revealed a set of lncRNAs that participated in inflammation and oxidative stress response pathways by regulating genes in cis or in trans. Finally, APOC1P1, PVT1, and LPAL2 were validated to regulate the migration and some pivotal inflammation genes under the CCA pathogenesis. Conclusions Our findings are the first to show that lncRNAs may not only be potential biomarkers of CCA progression but also respond to inflammation in CCA. |
| first_indexed | 2024-12-10T21:52:11Z |
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| institution | Directory Open Access Journal |
| issn | 1471-2164 |
| language | English |
| last_indexed | 2024-12-10T21:52:11Z |
| publishDate | 2018-10-01 |
| publisher | BMC |
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| series | BMC Genomics |
| spelling | doaj.art-cc277ec8e7d94444895fa4fd508e56412022-12-22T01:32:09ZengBMCBMC Genomics1471-21642018-10-0119111310.1186/s12864-018-5133-8Global identification and characterization of lncRNAs that control inflammation in malignant cholangiocytesBo-Wei Han0Hua Ye1Pan-Pan Wei2Bo He3Cai Han4Zhen-Hua Chen5Yue-Qin Chen6Wen-Tao Wang7MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory for Biocontrol, Sun Yat-sen UniversityDepartment of Hepatobiliary, and Department of Anesthesiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityMOE Key Laboratory of Gene Function and Regulation, State Key Laboratory for Biocontrol, Sun Yat-sen UniversityDepartment of Hepatobiliary, and Department of Anesthesiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityMOE Key Laboratory of Gene Function and Regulation, State Key Laboratory for Biocontrol, Sun Yat-sen UniversityMOE Key Laboratory of Gene Function and Regulation, State Key Laboratory for Biocontrol, Sun Yat-sen UniversityMOE Key Laboratory of Gene Function and Regulation, State Key Laboratory for Biocontrol, Sun Yat-sen UniversityMOE Key Laboratory of Gene Function and Regulation, State Key Laboratory for Biocontrol, Sun Yat-sen UniversityAbstract Background Long noncoding RNAs (lncRNAs) are known to play important roles in different cell contexts, including cancers. However, little is known about lncRNAs in cholangiocarcinoma (CCA), a cholangiocyte malignancy with poor prognosis, and associated with chronic inflammation and damage to the biliary epithelium. This study determined whether lncRNAs were dysregulated and participated in disease diagnosis or pivotal inflammation pathways through a genome-wide lncRNA screening and functional analysis. Results We firstly identified a large number of lncRNAs abnormally expressed between 9 pairs of cancerous and adjacent tissues of CCA, and between intra-hepatic CCA and extra-hepatic CCA through a genome-wide profiling. A set of aberrant differentially expressed lncRNAs were further validated in a training set (16 pairs) and a test set (11 pairs) of CCA patient samples. Following assessment of the diagnostic value of the 7 differentially expressed lncRNAs, we confirmed the optimal combination of H19, C3P1, AC005550.3, PVT1, and LPAL2 with area under the curve of 0.8828 [95% CI: 0.7441–1.021, P < 0.001], with 93.75% sensitivity and 81.25% specificity, at the cutoff point of − 0.2884 to distinguish the CCA tissue from the normal ones, suggesting that specific lncRNAs may have potential for detecting CCA. More importantly, the genome-wide locus and lncRNA/mRNA co-expression analyses revealed a set of lncRNAs that participated in inflammation and oxidative stress response pathways by regulating genes in cis or in trans. Finally, APOC1P1, PVT1, and LPAL2 were validated to regulate the migration and some pivotal inflammation genes under the CCA pathogenesis. Conclusions Our findings are the first to show that lncRNAs may not only be potential biomarkers of CCA progression but also respond to inflammation in CCA.http://link.springer.com/article/10.1186/s12864-018-5133-8CCAlncRNAGenome-wideDiagnostic valueInflammatory pathway |
| spellingShingle | Bo-Wei Han Hua Ye Pan-Pan Wei Bo He Cai Han Zhen-Hua Chen Yue-Qin Chen Wen-Tao Wang Global identification and characterization of lncRNAs that control inflammation in malignant cholangiocytes BMC Genomics CCA lncRNA Genome-wide Diagnostic value Inflammatory pathway |
| title | Global identification and characterization of lncRNAs that control inflammation in malignant cholangiocytes |
| title_full | Global identification and characterization of lncRNAs that control inflammation in malignant cholangiocytes |
| title_fullStr | Global identification and characterization of lncRNAs that control inflammation in malignant cholangiocytes |
| title_full_unstemmed | Global identification and characterization of lncRNAs that control inflammation in malignant cholangiocytes |
| title_short | Global identification and characterization of lncRNAs that control inflammation in malignant cholangiocytes |
| title_sort | global identification and characterization of lncrnas that control inflammation in malignant cholangiocytes |
| topic | CCA lncRNA Genome-wide Diagnostic value Inflammatory pathway |
| url | http://link.springer.com/article/10.1186/s12864-018-5133-8 |
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