scholarly journals Comprehensive Analysis of Differentially Expressed Long Noncoding RNA-mRNA in the Adenoma-Carcinoma Sequence of DNA Mismatch Repair Proficient Colon Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Wenkun Li ◽  
Qian Li ◽  
Jiang Ge ◽  
Yun Wang ◽  
Nanshan Li ◽  
...  

DNA proficient mismatch repair colon cancer (pMMR CC) is the most common subtype of sporadic CC. We aimed to investigate the role of long noncoding RNAs (lncRNAs) in pMMR CC carcinogenesis. In the present study, we conducted transcriptomic analysis of lncRNAs-mRNAs in five low-grade intraepithelial neoplasia (LGIN), five high-grade intraepithelial neoplasia (HGIN), four pMMR CC, and five normal control (NC) tissues. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathway, and coexpression network analyses were performed to elucidate the functions of lncRNAs and mRNAs as well as their interactions. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate five dysregulated lncRNAs in a large set of colon tissues. Receiver-operating characteristic (ROC) curves were employed to evaluate the performance of the candidate lncRNAs. A set of 5783 differentially expressed lncRNAs and 4483 differentially expressed mRNAs were detected among the LGIN, HGIN, pMMR CC, and NC samples. These differentially expressed lncRNAs and mRNAs were assigned to 275 significant GO terms and 179 significant KEGG enriched pathways. qRT-PCR confirmed that the expression of five selected lncRNAs (ENST00000521815, ENST00000603052, ENST00000609220, NR_026543, and ENST00000545920) were consistent with the microarray data. ROC analysis showed that four lncRNAs (ENST00000521815, ENST00000603052, ENST00000609220, and NR_026543) had larger area under the ROC curve (AUC) values compared to serum carcinoembryonic antigens, thereby distinguishing NC from pMMR CC. In conclusion, several lncRNAs play various roles in the adenoma-carcinoma sequence and may serve as potential biomarkers for the early diagnosis of pMMR CC.

2020 ◽  
Author(s):  
Wenkun Li ◽  
Qian Li ◽  
Jiang Ge ◽  
Yun Wang ◽  
Nanshan Li ◽  
...  

Abstract Background DNA mismatch repair proficient colon cancer (pMMR CC) is the most common subtype of sporadic CC. However, the role of long non-coding RNAs (lncRNAs) in pMMR CC carcinogenesis has not been fully elucidated. Methods In the present study, we conducted transcriptomic analysis of lncRNAs-mRNAs in five low-grade intraepithelial neoplasia (LGIN), five high-grade intraepithelial neoplasia (HGIN), four pMMR CC, and five normal control (NC) tissues. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathway, and Co-Expression Network analyses were performed to elucidate the functions of lncRNAs and mRNAs as well as their interactions. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate five dysregulated lncRNAs in a large set of colon tissues. Receiver-operating characteristic (ROC) curves were employed to evaluate the performance of the candidate lncRNAs. Results A set of 5783 differentially expressed lncRNAs and 4483 differentially expressed mRNAs were detected among the LGIN, HGIN, pMMR CC, and NC samples. These differentially expressed lncRNAs and mRNAs were assigned to 275 significant GO terms and 179 significant KEGG enriched pathways. qRT-PCR confirmed that the expression of five selected lncRNAs (ENST00000521815, ENST00000603052, ENST00000609220, NR_026543, and ENST00000545920) were consistent with the microarray data. ROC analysis showed that four lncRNAs (ENST00000521815, ENST00000603052, ENST00000609220, and NR_026543) had larger area under the ROC curve (AUC) values than serum carcinoembryonic antigens, thereby distinguishing NC from pMMR CC. Conclusions Several lncRNAs play various roles in the adenoma–carcinoma sequence and may serve as potential biomarkers for the early diagnosis of pMMR CC.


2020 ◽  
Author(s):  
Wenkun Li ◽  
Qian Li ◽  
Jiang Ge ◽  
Yun Wang ◽  
Nanshan Li ◽  
...  

Abstract Background DNA mismatch repair proficient colon cancer (pMMR CC) is the most common subtype of sporadic CC. We aimed to investigate the role of long non-coding RNAs (lncRNAs) in pMMR CC carcinogenesis. Methods In the present study, we conducted transcriptomic analysis of lncRNAs-mRNAs in five low-grade intraepithelial neoplasia (LGIN), five high-grade intraepithelial neoplasia (HGIN), four pMMR CC, and five normal control (NC) tissues. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathway, and Co-Expression Network analyses were performed to elucidate the functions of lncRNAs and mRNAs as well as their interactions. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate five dysregulated lncRNAs in a large set of colon tissues. Receiver-operating characteristic (ROC) curves were employed to evaluate the performance of the candidate lncRNAs. Results A set of 5783 differentially expressed lncRNAs and 4483 differentially expressed mRNAs were detected among the LGIN, HGIN, pMMR CC, and NC samples. These differentially expressed lncRNAs and mRNAs were assigned to 275 significant GO terms and 179 significant KEGG enriched pathways. qRT-PCR confirmed that the expression of five selected lncRNAs (ENST00000521815, ENST00000603052, ENST00000609220, NR_026543, and ENST00000545920) were consistent with the microarray data. ROC analysis showed that four lncRNAs (ENST00000521815, ENST00000603052, ENST00000609220, and NR_026543) had larger area under the ROC curve (AUC) values than serum carcinoembryonic antigens, thereby distinguishing NC from pMMR CC. Conclusions Several lncRNAs play various roles in the adenoma–carcinoma sequence and may serve as potential biomarkers for the early diagnosis of pMMR CC.


2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Dongyun Lei ◽  
Lechun Lv ◽  
Li Yang ◽  
Wenjuan Wu ◽  
Yong Liu ◽  
...  

Chronic actinic dermatitis (CAD), a photosensitive dermatosis, is characterized by inflammatory lesions, especially on sun-exposed skin. However, its pathogenesis remains unclear. In this study, second-generation RNA sequencing and comprehensive bioinformatics analyses of mRNAs and long noncoding RNAs (lncRNAs) were performed to determine the transcriptome profiles of patients with CAD. A total 6889 annotated lncRNAs, 341 novel lncRNAs, and 65091 mRNAs were identified. Interestingly, patients with CAD and healthy controls showed distinct transcriptome profiles. Indeed, 198 annotated (81.48%) and 45 novel (18.52%) lncRNAs were differentially expressed between the two groups. GO, KEGG, and RGSEA analyses of lncRNAs showed that inflammatory and immune response related pathways played crucial roles in the pathogenetic mechanism of CAD. In addition, we unveiled key differentially expressed lncRNAs, including lncRNA RP11-356I2.4 which plays a role probably by regulating TNFAIP3 and inflammation. qRT-PCR data validated the differentially expressed genes. The newly identified lncRNAs may have potential roles in the development of CAD; these findings lay a solid foundation for subsequent functional exploration of lncRNAs and mRNAs as therapeutic targets for CAD.


2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Ling-zhao Meng ◽  
Ju-gao Fang ◽  
Jing-wu Sun ◽  
Fan Yang ◽  
Yong-xiang Wei

Objectives. This study aimed to identify aberrantly expressed long noncoding RNAs (lncRNAs) profile of sinonasal squamous cell carcinoma (SSCC) and explore their potential functions. Methods. We investigated lncRNA and mRNA expression in SSCC and paired adjacent noncancerous tissues obtained from 6 patients with microarrays. Gene ontology (GO) analysis and pathway analysis were utilized to investigate the gene function. Gene signal-network and lncRNA-mRNA network were depicted. Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to validate 5 lncRNAs in a second set of paired SSCC and adjacent noncancerous tissues obtained from 22 additional patients. Results. We identified significantly differentially expressed lncRNAs (n=3146) and mRNAs (n=2208) in SSCC relative to noncancerous tissues. The GO annotation indicated that there are some core gene products that may be attributed to the progress of SSCC. The pathway analysis identified many pathways associated with cancer. The results of lncRNA-mRNA network and gene signal-network implied some core lncRNAs/mRNAs might play important roles in SSCC pathogenesis. The results of qRT-PCR showed that all of the 5 lncRNAs were differentially expressed and consistent with the microarray results. Conclusion. Our study is the first screening and analysis of lncRNAs expression profile in SSCC and may offer new insights into pathogenesis of this disease.


2019 ◽  
Vol 89 (3) ◽  
pp. 455-463 ◽  
Author(s):  
Hao Liu ◽  
Yiping Huang ◽  
Yingying Zhang ◽  
Yineng Han ◽  
Yixin Zhang ◽  
...  

ABSTRACT Objectives: To investigate the long noncoding RNA (lncRNA) expression profile of cementoblasts under compressive force. Materials and Methods: Mouse cementoblasts were exposed to compression (1.5 g/cm2) for 8 hours. RNA sequencing (RNA-seq) was performed to compare the transcriptomes of the compressed and control cells. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate five of the differentially expressed lncRNAs of interest. Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were also performed. Results: A total of 70 lncRNAs and 521 mRNAs were differentially regulated in cementoblasts subjected to compressive loading. Among the differentially expressed lncRNAs, 57 were upregulated and 13 downregulated. The expression levels of the five selected lncRNAs (Prkcz2, Hklos, Trp53cor1, Gdap10, and Ak312-ps) were validated by qRT-PCR and consistent with the RNA-seq results. GO functional annotation demonstrated upregulation of genes associated with cellular response to hypoxia and apoptotic processes during compressive loading. KEGG analysis identified the crucial pathways involving the hypoxia-inducing factor-1α, forkhead box O, and mammalian target of rapamycin signaling pathways. Conclusions: Mechanical compression changes the lncRNA expression profile of cementoblasts, providing important references for further investigation into the role and regulation of lncRNAs in compressed cementoblasts and root resorption during orthodontic treatment.


2016 ◽  
Vol 43 (8) ◽  
pp. 1523-1531 ◽  
Author(s):  
Zhongyu Xie ◽  
Jinteng Li ◽  
Peng Wang ◽  
Yuxi Li ◽  
Xiaohua Wu ◽  
...  

Objective.We previously demonstrated that mesenchymal stem cells (MSC) from patients with ankylosing spondylitis (AS; ASMSC) have a greater osteogenic differentiation capacity than MSC from healthy donors (HDMSC) and that this difference underlies the pathogenesis of pathological osteogenesis in AS. Here we compared expression levels of long noncoding RNA (lncRNA) and mRNA between osteogenically differentiated ASMSC and HDMSC and explored the precise mechanism underlying abnormal osteogenic differentiation in ASMSC.Methods.HDMSC and ASMSC were induced with osteogenic differentiation medium for 10 days. Microarray analyses were then performed to identify lncRNA and mRNA differentially expressed between HDMSC and ASMSC, which were then subjected to bioinformatics analysis and confirmed by quantitative real-time PCR (qRT-PCR) assays. In addition, coding-non-coding gene co-expression (CNC) networks were constructed to examine the relationships between the lncRNA and mRNA expression patterns.Results.A total of 520 lncRNA and 665 mRNA were differentially expressed in osteogenically differentiated ASMSC compared with HDMSC. Bioinformatics analysis revealed 64 signaling pathways with significant differences, including transforming growth factor-β signaling. qRT-PCR assays confirmed the reliability of the microarray data. The CNC network indicated that 4 differentially expressed lncRNA, including lnc-ZNF354A-1, lnc-LIN54-1, lnc-FRG2C-3, and lnc-USP50-2 may be involved in the abnormal osteogenic differentiation of ASMSC.Conclusion.Our study characterized the differential lncRNA and mRNA expression profiles of osteogenically differentiated ASMSC and identified 4 lncRNA that may participate in the abnormal osteogenic differentiation of ASMSC. These results provide insight into the pathogenesis of pathological osteogenesis in AS.


2020 ◽  
Vol 9 (9) ◽  
pp. 2783
Author(s):  
Ana Torres-Do Rego ◽  
María Barrientos ◽  
Adriana Ortega-Hernández ◽  
Javier Modrego ◽  
Rubén Gómez-Gordo ◽  
...  

Patients with subaneurysmal aortic dilation (SAD; 25–29 mm diameter) are likely to progress to true abdominal aortic aneurysm (AAA). Despite these patients having a higher risk of all-cause mortality than subjects with aortic size <24 mm, early diagnostic biomarkers are lacking. MicroRNAs (miRs) are well-recognized potential biomarkers due to their differential expression in different tissues and their stability in blood. We have investigated whether a plasma miRs profile could identify the presence of SAD in high cardiovascular risk patients. Using qRT-PCR arrays in plasma samples, we determined miRs differentially expressed between SAD patients and patients with normal aortic diameter. We then selected 12 miRs to be investigated as biomarkers by construction of ROC curves. A total of 82 significantly differentially expressed miRs were found by qPCR array, and 12 were validated by qRT-PCR. ROC curve analyses showed that seven selected miRs (miR-28-3p, miR-29a-3p, miR-93-3p, miR-150-5p, miR-338-3p, miR-339-3p, and miR-378a-3p) could be valuable biomarkers for distinguishing SAD patients. MiR-339-3p showed the best sensitivity and specificity, even after combination with other miRs. Decreased miR-339-3p expression was associated with increased aortic abdominal diameter. MiR-339-3p, alone or in combination with other miRs, could be used for SAD screening in high cardiovascular risk patients, helping to the early diagnosis of asymptomatic AAA.


2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Dao-xiong Ye ◽  
Si-si Wang ◽  
Ying Huang ◽  
Pan Chi

Abstract Background Circular RNAs (circRNAs), a novel type of noncoding RNAs, play critical roles in the initiation and progression of cancer. Emerging studies also shows that circRNAs may function as potential markers for cancer diagnosis and treatment. However, the diagnostic value of circRNAs in colorectal cancer (CRC) remains need to be unearthed. Methods CircRNA microarray was performed to detect the differentially expressed circRNAs in eight plasma samples, including four colorectal cancer (CRC) and four normal samples. Besides, the results of microarray were validated by quantitative real-time polymerase chain reaction (qRT-PCR). Moreover, ROC curve evaluation was performed to calculate the diagnostic value of significantly dysregulated circRNAs. In order to predict the potential mechanism of the significant circRNAs, circRNA–miRNA–mRNA network was constructed based on the TargetScan, miRTarBase and MIRDB database, as well as CircInteractome online software. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to further predict the function of meaningful circRNAs. Results Totally three differentially expressed circRNAs were identified in CRC plasma compared to normal plasma by circRNA microarray analysis, and the results was validated by qRT-PCR. Hsa_circ_0082182, hsa_circ_0000370 and hsa_circ_0035445 were identified and ROC curves analysis was used to calculate the single and joint diagnostic value. Furthermore, GO and KEGG analyses revealed that functions were mainly cancer-related, which indicated that the circRNAs were meaningfully associated with CRC cell proliferation and metastasis. Conclusion In conclusion, we have identified three circRNAs that are dysregulated in CRC plasma, including hsa_circ_0082182, hsa_circ_0000370 and hsa_circ_0035445. ROC curves showed that these circRNAs might have diagnostic value for colorectal cancer. Furthermore, bioinformatics analysis indicated that the above-mentioned circRNAs might be involved in the development of CRC.


2020 ◽  
Author(s):  
Jie Song ◽  
Weiyu Li ◽  
Yajie Hu ◽  
Hui Li ◽  
Huiwen Zheng ◽  
...  

Abstract Background: Enterovirus 71 (EV-A71) and coxsackievirus A16 (CV-A16) are the major pathogens responsible for hand, foot and mouth disease (HFMD), but the detailed mechanism caused by the two viruses remains unclear. Methods: In this study, we aimed to adopt transcriptome sequencing technology to investigate changes in the transcriptome profiles after infection with EV-A71 and CV-A16 in human bronchial epithelial (16HBE) cells. Results: Through systematic bioinformatics analysis, we then searched for useful clues regarding the pathogenesis of HFMD. As a result, a total of 111 common differentially expressed genes were present in both the EV-A71- and CV-A16-infected groups. A trend analysis of these 111 genes showed that there were 91 genes displaying the same trend in the EV-A71 and CV-A16 infection groups, including 49 upregulated genes and 42 downregulated genes. These 91 genes were further used to conduct GO, pathway, and coexpression network analyses. It was discovered that the enriched GO terms (such as Histone acetylation and positive regulation of phosphorylation) and pathways (such as glycosylphosphatidylinositol (GPI)-anchor biosynthesis and DNA replication) might be closely associated with the pathogenic mechanism of the two viruses, and key genes (such as TBCK and GPC) might be involved in the progression of HFMD. Finally, we randomly selected 10 differentially expressed genes for qRT-PCR to validate the transcriptome sequencing data. The experimental qRT-PCR results were roughly in agreement with the results of transcriptome sequencing. Conclusions: Collectively, our results provide clues for the pathogenesis of HFMD induced by EV-A71 and CV-A16.


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