Cluster mir-17–92 is differentially expressed in colon cancer patients and embryonic colon tissue and may contribute to carcinogenesis through E2F1 expression

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 10525-10525
Author(s):  
J. Garcia-Foncillas ◽  
A. Navarro ◽  
E. Bandres ◽  
R. Artells ◽  
I. Moreno ◽  
...  

10525 Background: Mature microRNAs (miRNA) are small RNA molecules that act as negative regulators of gene expression, either inhibiting mRNA by blocking its translation into protein or destroying it by RNA interference. Many miRNAs participate in essential processes, including normal embryonic development and carcinogenesis. Methods: We have assessed 156 mature miRNAs in colon tissue from eleven 7–12-week human embryos and 44 colorectal human samples. Data were analyzed using TIGR Multiexperiment viewer. Two multivariate permutation test were performed. Potential target genes of differentially expressed miRNAs are evaluated by western blot. Results: 28 miRNAs were expressed in stage I tumor tissue but not in the corresponding normal tissue, and 13 of these 28 miRNAs (46%) were also expressed in embryonic tissue. Sixty-four miRNAs were differentially expressed in stage II tumor tissue, and 29 of these 64 miRNAs (45%) were also expressed in embryonic tissue. Some miRNAs that are active during embryogenesis, such as mir-17–92, miR-181a, miR-181b and miR-181c (linked to HOXA11), and miR-10a (linked to HOXB8)23, are also expressed during tumor growth. The analysis of 156 miRNAs by K-means support revealed two well-differentiated groups: the embryos of 7–8 weeks and those of 9–12 weeks. Lower miRNA expression was also observed in tumor tissue from stage I in comparison with stage II disease (P=0.014). Analysis of potential target genes revealed that cluster mir-17–92 is differentially expressed in colon cancer and embryonic tissue and may contribute to carcinogenesis through E2F1 expression. Conclusions: Our findings indicate that miRNAs expressed during the embryonic development of the human colon are also expressed in colon tumor tissue. During colon organogenesis, miRNA expression is at first high, while cells are still undifferentiated, but expression levels decrease as cells become more differentiated. In contrast, during the development of colorectal cancer, this process is reversed. No significant financial relationships to disclose.

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3311
Author(s):  
Diego Marques ◽  
Layse Raynara Ferreira-Costa ◽  
Lorenna Larissa Ferreira-Costa ◽  
Ana Beatriz Bezerra-Oliveira ◽  
Romualdo da Silva Correa ◽  
...  

The aberrant expression of microRNAs in known to play a crucial role in carcinogenesis. Here, we evaluated the miRNA expression profile of sigmoid colon cancer (SCC) compared to adjacent-to-tumor (ADJ) and sigmoid colon healthy (SCH) tissues obtained from colon biopsy extracted from Brazilian patients. Comparisons were performed between each group separately, considering as significant p-values < 0.05 and |Log2(Fold-Change)| > 2. We found 20 differentially expressed miRNAs (DEmiRNAs) in all comparisons, two of which were shared between SCC vs. ADJ and SCC vs. SCH. We used miRTarBase, and miRTargetLink to identify target-genes of the differentially expressed miRNAs, and DAVID and REACTOME databases for gene enrichment analysis. We also used TCGA and GTEx databases to build miRNA-gene regulatory networks and check for the reproducibility in our results. As findings, in addition to previously known miRNAs associated with colorectal cancer, we identified three potential novel biomarkers. We showed that the three types of colon tissue could be clearly distinguished using a panel composed by the 20 DEmiRNAs. Additionally, we found enriched pathways related to the carcinogenic process in which miRNA could be involved, indicating that adjacent-to-tumor tissues may be already altered and cannot be considered as healthy tissues. Overall, we expect that these findings may help in the search for biomarkers to prevent cancer progression or, at least, allow its early detection, however, more studies are needed to confirm our results.


2016 ◽  
Vol 17 (5) ◽  
pp. 656 ◽  
Author(s):  
Antonina Parafioriti ◽  
Caterina Bason ◽  
Elisabetta Armiraglio ◽  
Lucia Calciano ◽  
Primo Daolio ◽  
...  

2013 ◽  
Vol 25 (1) ◽  
pp. 251 ◽  
Author(s):  
S. Seifi Noferesti ◽  
M. Hoelker ◽  
M. H. Sohel ◽  
D. Salilew-Wondim ◽  
F. Rings ◽  
...  

MicroRNAs (miRNA) are noncoding small RNA that are known to play a role in posttranscriptional regulation of genes involved in various physiological processes including disease and reproduction. The circulatory forms of miRNA, which are present in body fluids, are reported to be used as biomarkers for disease and pregnancy. This study was conducted to investigate the effect of ovarian hyperstimulation on the expression pattern of circulatory miRNA in blood plasma and follicular fluid. For this, one group of Simmental heifers (n = 6) was hyper-stimulated using a superovulation (SO) protocol of 8 consecutive FSH injections over 4 days in decreasing doses, and others (n = 6) were synchronized (SY) using a standard synchronization protocol. Following this, the blood samples were collected at Day 0 (onset of oestrus) and Day 7, and follicular fluid was collected from both groups at Day 0 of the oestrous cycle. Total RNA, including small RNA, was then isolated from follicular fluid and blood plasma using a miRNeasy mini kit (Qiagen, Valencia, CA, USA) and subsequently used for circulatory miRNA expression studies using the human miRCURY LNA™ Universal RT miRNA PCR array system (Exiqon, Woburn, MA, USA). Following the miRNA PCR array run, data analysis was performed using a delta threshold cycle (ΔCT) method. Results showed that 23 miRNAs were found to be differentially expressed in blood plasma (fold change ≥2 and P ≤ 0.05) between SO and SY groups. Among these, 8 miRNAs including miR-127-3p, miR-494, miR-147, miR-134, and miR-153 were downregulated and 15 miRNAs including miR-34a, miR-103, miR-181c, miR-24-2-3p, miR-18a-3p, miR-20b-3p, and miR-708-3p were found to be upregulated in SO groups. Similarly, in follicular fluid, 71 miRNAs were found to be differentially expressed between the SO and SY groups. Of these, 33 miRNA including miR-100, miR-877, miR-659, miR-200c, miR-29b-2-3p, miR-361-5p, and miR-145 were downregulated, whereas 38 miRNAs including miR-374a, miR-720, miR-155-3p, miR-202-3p, miR-33b, miR-12-3p, and miR-224-3p were upregulated in follicular fluid aspirated from SO cows compared with the SY animals. Ingenuity pathway analysis of predicted target genes of miRNA, which are dysregulated due to ovarian hyperstimulation, showed the dominance of pathways related to neuregulin signalling, axonal guidance signalling, GNRH signalling, and Wnt β-catenin signalling pathways. In conclusion, this study revealed alternation in circulatory miRNA expression profile both in blood plasma and follicular fluid as a result of ovarian hyperstimulation.


2020 ◽  
Vol 71 (1) ◽  
pp. 37-47
Author(s):  
Liyun Wang ◽  
Shaogang Li ◽  
Lele Xu ◽  
Yongqin Li ◽  
Huaxu Chen ◽  
...  

Abstract The Japanese spineless cuttlefish (Sepiella japonica) is an important economic species and model animal. Many studies suggested that microRNAs (miRNAs) play an important regulatory role in the embryonic development of this species. However, comparative miRNA profiles during embryogenesis of cuttlefish have not been reported before. Therefore, in this study, miRNA profiles were obtained from embryos of S. japonica from eye primordium formation to larval growing stage by miRNA sequencing. A total of 1528 known miRNAs and 203 novel miRNAs were identified during different development stages. Among which, 62 differentially expressed miRNAs among different development stages were identified. GO analysis indicated that the potential target genes for these differentially expressed miRNAs were involved in many GO terms including intracellular membrane-bounded organelle, cell morphogenesis, regulation of developmental process, etc. In addition, miRNA-mRNA network analysis indicated that many of the target genes of these differentially expressed miRNAs were involved in integral component of the membrane. In conclusion, our work provided a global view of miRNA expression profiles during embryonic development of S. japonica.


Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1032
Author(s):  
Pamela Pignatelli ◽  
Lorena Iezzi ◽  
Martina Pennese ◽  
Paolo Raimondi ◽  
Anna Cichella ◽  
...  

Background. Intestinal microbiota dysbiosis may enhance the carcinogenicity of colon cancer (CC) by the proliferation and differentiation of epithelial cells. Oral Fusobacterium nucleatum (Fn) and Porphyromonas gingivalis (Pg) have the ability to invade the gut epithelium, promoting tumor progression. The aim of the study was to assess whether the abundance of these odontopathogenic bacteria was associated with colon cancer. We also investigated how lifestyle factors could influence the oral Fn and Pg abundance and CC. Methods. Thirty-six CC patients were included in the study to assess the Pg and Fn oral and colon tissue abundance by qPCR. Oral health data, food habits and lifestyles were also recorded. Results. Patients had a greater quantity of Fn in the oral cavity than matched CC and adjacent non-neoplastic mucosa (adj t) tissues (p = 0.004 and p < 0.001). Instead, Pg was not significantly detected in colonic tissues. There was an association between the Fn quantity in the oral and CC tissue and a statistically significant relation between the Fn abundance in adenocarcinoma (ADK) and staging (p = 0.016). The statistical analysis revealed a tendency towards a greater Fn quantity in CC (p = 0.073, η2p = 0.12) for high-meat consumers. Conclusion. In our study, Pg was absent in colon tissues but was correlated with the oral inflammation gingival and plaque indices. For the first time, there was evidence that the Fn oral concentration can influence colon tissue concentrations and predict CC prognosis.


Reproduction ◽  
2019 ◽  
Vol 157 (6) ◽  
pp. 525-534 ◽  
Author(s):  
Hang Qi ◽  
Guiling Liang ◽  
Jin Yu ◽  
Xiaofeng Wang ◽  
Yan Liang ◽  
...  

MicroRNA (miRNA) expression profiles in tubal endometriosis (EM) are still poorly understood. In this study, we analyzed the differential expression of miRNAs and the related gene networks and signaling pathways in tubal EM. Four tubal epithelium samples from tubal EM patients and five normal tubal epithelium samples from uterine leiomyoma patients were collected for miRNA microarray. Bioinformatics analyses, including Ingenuity Pathway Analysis (IPA), Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, were performed. Quantitative real-time polymerase chain reaction (qRT-PCR) validation of five miRNAs was performed in six tubal epithelium samples from tubal EM and six from control. A total of 17 significantly differentially expressed miRNAs and 4343 potential miRNA-target genes involved in tubal EM were identified (fold change >1.5 and FDR-adjustedPvalue <0.05). IPA indicated connections between miRNAs, target genes and other gynecological diseases like endometrial carcinoma. GO and KEGG analysis revealed that most of the identified genes were involved in the mTOR signaling pathway, SNARE interactions in vesicular transport and endocytosis. We constructed an miRNA-gene-disease network using target gene prediction. Functional analysis showed that the mTOR pathway was connected closely to tubal EM. Our results demonstrate for the first time the differentially expressed miRNAs and the related signal pathways involved in the pathogenesis of tubal EM which contribute to elucidating the pathogenic mechanism of tubal EM-related infertility.


2021 ◽  
Author(s):  
Jiacong Peng ◽  
Xiaohong Peng ◽  
Ying Wang ◽  
Liping Jiang ◽  
Dayu Li ◽  
...  

Abstract BackgroundMalaria, caused by Plasmodium, is one of the three major infectious diseases that se­riously endangers public health. Resistance to an­ti-malarial drugs and insecticides has made the prevention and control of malar­ia shown little improvement in the last four years. This study aimed to explore the changes in microRNA (miRNA) expression profiling of malaria patient and predict malaria-related miRNA by bioinformatics methods to provide theoretical basis for further verification of the correlation between specific miRNAs and immune regulation of malaria.MethodsSerum of patients infected by Plasmodium falciparum and healthy people from Myanmar border area was collected. miRNA expression profiling was obtained by RT-qPCR. Then the differentially expressed miRNA was screened and target genes were predicted by four miRNA databases (TargetScan, DIANA-microT, miRDB, and miRTarbase) and an intersection of target genes was obtained by Venn analysis. GO and KEGG analysis were performed for the overlapping target genes via Metascape. The results were further visualized by Cytoscape. Finally, Protein-protein interaction (PPI) network of predicted overlapping target genes was built by STRING.ResultsAmong the 341 tested serum miRNAs, 64 were differentially expressed in malaria patients (P<0.05), 27 miRNAs were up-regulated and 37 miRNAs were down-regulated. The miRNA with the most significant difference was hsa-miR-106b-5p (FC=14.871, adjusted.P.value<0.01); GO and KEGG analysis found that its overlapping predicted target gene set was remarkably enriched in biological functions such as GO:0007264~small GTPase mediated signal transduction, GO:0051056~regulation of small GTPase mediated signal transduction, GO:0051020~GTPase binding, GO:0048514~blood vessel morphogenesis(P<0.01) and signal pathway such as hsa04144: Endocytosis, hsa01521:EGFR tyrosine kinase inhibitor resistance, hsa05212:Pancreatic cancer (P<0.01); Besides, a PPI network containing 39 predicted target genes of hsa-miR-106b-5p was constructed, and 5 hub genes VEGFA, STAT3, RACGAP1, OCRL, and RBBP7 have been selected.ConclusionThe bioinformatics analysis results indicated that hsa-miR-106b-5p has a great relationship with malaria, it plays a part in inhibiting the emergence of ARTs resistance in Plasmodium and tumor progression, which may be achieved by regulating vascular morphogenesis, endocytosis, and VEGFA. The underlying mechanism needs to be further elucidated. We believe that this finding will facilitate an in-depth research on the as­sociation between malaria and miRNA.


2010 ◽  
Vol 345 (1-2) ◽  
pp. 283-290 ◽  
Author(s):  
Xiao-Yan Wang ◽  
Ming-Hua Wu ◽  
Fen Liu ◽  
Yu Li ◽  
Nan Li ◽  
...  

2018 ◽  
Vol 49 (5) ◽  
pp. 2088-2098 ◽  
Author(s):  
Yu Chen ◽  
Yanling Wu ◽  
Haiqiang Yao ◽  
Hui Luo ◽  
Bing Lin ◽  
...  

Background/Aims: Based on the theory of constitution in Traditional Chinese Medicine (TCM), the Chinese Han population has been classified into nine constitutions. Of these, Yang deficiency constitution mainly exhibit cold intolerance while Yin deficiency constitution mainly exhibit heat intolerance. Some studies have been carried out to explore the modern genetic and biological basis of such constitution classification, but more remains to be done. MicroRNA (miRNA) serves as post-transcriptional regulators of gene expression and may play a role in the classification process. Here, we examined miRNA expression profile of saliva to further improve the comprehensiveness of constitution classification. Methods: Saliva was collected from Chinese Han individuals with Yang deficiency, Yin deficiency and Balanced constitutions (n=5 each), and miRNA expression profile was determined using the Human miRNA OneArray®v7. Based on 1.5 Fold change, means log2|Ratio|≥0.585 and P-value< 0.05, differentially expressed miRNA was screened. Target genes were predicted using DIANA-TarBasev7.0 and analysis of KEGG pathway was carried out using DIANA-mirPathv.3. Results: We found that 81 and 98 differentially expressed miRNAs were screened in Yang deficiency and Yin deficiency constitution, respectively. Among them, 16 miRNAs were identical and the others were unique. In addition, the target genes that are regulated by the unique miRNAs were significantly enriched in 27 and 20 signaling pathways in Yang deficiency and Yin deficiency constitution, respectively. Thyroid hormone signaling pathway is present in both constitutions. These unique miRNAs that regulated target genes of thyroid hormone signaling pathway may be associated with cold intolerance or heat intolerance. Conclusion: The results of our study show that Yang deficiency and Yin deficiency constitutions exhibit systematic differences in miRNA expression profile. Moreover, the distinct characteristics of TCM constitution may be explained, in part, by differentially expressed miRNAs.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13516-e13516
Author(s):  
Inna A. Novikova ◽  
Natalya N. Timoshkina ◽  
Oleg Ivanovich Kit ◽  
Sergey I. Poluektov ◽  
Andrey V. Dashkov ◽  
...  

e13516 Background: The colorectal cancer (CRC) incidence is steadily increasing. Moreover, the problem of its early diagnosis remains unresolved due to the low specificity of known tumor markers, and the problem of creating new therapeutic approaches is due to the lack of a complete understanding of the mechanisms of regulation of gene expression in this oncopathology. The study of micro-RNAs (short non-coding RNAs that regulate gene expression) can be the solution to both problems. The aim of the study was to analyze micro-RNA differential expression in the tumor and non-tumor tissues of CRC patients. Methods: 5 patients with CRC (colon adenocarcinoma, G2) were selected for the multiple parallel micro-RNA sequencing. The mirVana miRNA Isolation Kit protocol was used to isolate small RNA fractions. The miRNA library was prepared using the TruSeq Small RNASample Preparation Kit. Sequencing of the nucleotide sequences of cDNA libraries was performed using a MiSeq (Illumina, USA). The copy numbers of micro-RNA were determined by comparing the nucleotide sequence of the sequenced molecules in each sample with the known nucleotide sequences of micro-RNA presented in the databases. When analyzing the differential expression of micro-RNA, the DESeq2 method implemented in R medium was used. Results: Six differentially expressed micro-RNAs were detected (p < 0.05): 2 that decrease expression (hsa-miR-143-3p,hsa-miR-26a-5p) and 4 increase expression in the tumor relative to non-tumor (hsa-miR-25-3p, hsa-miR-92a-3p, hsa-miR-21-5p, hsa-let-7i-5p). The highest level of expression in both tumor and non-tumor tissue was observed for hsa-miR-143-3p, the lowest one for hsa-let-7i-5p. Moreover, the largest difference in micro-RNA expression in tumor tissue relative to non-tumor was shown for hsa-miR-92a-3p (4.5 times, p = 0.02), the smallest for hsa-miR-143-3p (2.4 times, p = 0.04). For miRNAs that differentially changed their expression, a search was made for target genes using the miRWalk 3.0 database. 14573 target genes were found, of which 3346 were for hypo-expressed micro-RNAs and 11228 for hyper-expressed micro-RNAs. Conclusions: Sequencing revealed 6 differentially expressed micro-RNAs (hsa-miR-143-3p, hsa-miR-26a-5p, hsa-miR-25-3p, hsa-miR-92a-3p, hsa-miR-21-5p, hsa-let-7i-5p) in the tumor tissue is relatively non-tumor tissues of the colon. The data obtained expand the understanding of the mechanisms of gene regulation in the context of this oncopathology and may possibly become the basis for highly specific tumor markers panel.


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