Identification of differentially expressed circular RNAs in chemoresistant colorectal cancer

Epigenomics ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 875-884 ◽  
Author(s):  
Nadiah Abu ◽  
Kha Wai Hon ◽  
Shivapriya Jeyaraman ◽  
Azyani Yahaya ◽  
Nik MA Abdullah ◽  
...  
2021 ◽  
Author(s):  
Liyuan Liu ◽  
Shan Wu ◽  
Dan Jiang ◽  
Yuliang Qu ◽  
Hongxia Wang ◽  
...  

Abstract Background: Abnormal expression of Circular RNAs (circRNAs) occurs in the occurrence and progression of colorectal cancer (CRC) and plays an important role in the pathogenesis of tumors. We combined bioinformatics and laboratory-validated methods to search for key circRNAs and possible potential mechanisms. Methods: Colorectal cancer tissues and normal paracancerous tissues were detected by microarray analysis and qRT-PCR validation, and differentially expressed circRNAs were screened and identified. The circRNA-miRNA-mRNA regulatory network (cirReNET) was constructed, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to ascertain the functions of circRNAs in CRCs. In addition, a protein-protein interaction (PPI) network of hub genes which acquired by string and plugin app CytoHubba in cytoscape was established. Validation of expression of hub genes was identified by GEPIA database. Results: 564 differentially expressed circRNAs which include 207 up-regulated and 357 down-regulated circRNAs were detected. The top 3 up-regulated circRNAs (hsa_circRNA_100833, hsa_circRNA_103828, hsa_circRNA_103831) and the top 3 down-regulated circRNAs (hsa_circRNA_103752, hsa_circRNA_071106, hsa_circRNA_102293) in chip analysis were chosen to be verified in 33 pairs of CRCs by qRT-PCR. The cirReNET include of 6 circRNAs, 19 miRNAs and 210 mRNA. And the targeted mRNAs were associated with cellular metabolic process, cell cycle and glandular epithelial cell differentiation and so on. 12 and 10 target hub genes were shown separately in upregulated circRNA-downregulated miRNA-upregulated mRNA (UcDiUm-RNA) group and downregulated circRNA-upregulated miRNA-downregulated mRNA (DcUiDm-RNA) group. Finally, we may have predicted and discovered several critical circRNA-miRNA-mRNA regulatory axes (cirReAXEs) which may play important roles in colorectal cancer. Conclusion: We constructed a cirReNET including 6 candidate circRNAs, which were crucial in CRCs, may become potential diagnostic markers and predictive indicators of CRCs, and we may provide a research direction for the pathogenesis of colorectal cancer.


2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 230-230
Author(s):  
Manuel Valladares-Ayerbes ◽  
Carmen Garrigos ◽  
Miquel Taron ◽  
Angélica Figueroa ◽  
Enrique Aranda

230 Background: Circular RNAs (circRNAs) are emerging as essential regulators of cancer- related biological hallmarks, as cell proliferation, apoptosis, differentiation, immune regulation and angiogenesis. CircRNAs are abundant, conserved, and have a tissue‐specific expression pattern. These characteristics make them candidate to serve as biomarkers in liquid biopsy (LB) in cancer. The aim of this study is to analyse differential expression of circRNAs in the colorectal cancer (CRC) scenario. Methods: To comprehensively understand the expression patterns of circRNAs we characterized 13,617 circRNAs using a microarray [Arraystar v2 (8x15K)] in 10 human samples, five CRC cell lines, one colorectal human tumour, one normal colon healthy control, vs. Peripheral Human Blood Leukocytes (2 pools) and Human Bone Marrow. Differentially expressed circRNAs were identified using fold change (FC) cut-off or through Volcano Plot filtering respectively. CircRNAs having FC ▪2 and P-values ▪ 0.05 were selected. CircRNA/microRNA interaction was predicted with target prediction software. Results: Hierarchical clustering showed distinguishable circRNA expression profiling among 10 samples. These data indicated that circRNAs have a different expression pattern in colorectal tissues compared with that in blood and bone marrow tissues. The microarray data showed 2329 circRNAs differentially expressed (FC > 2.0, P < 0.05). Among them, 964 circRNAs were upregulated and 1365 were downregulated in colon tissues compared with blood and bone marrow. Using a stringent criterion (FC > 10, P≤ 0.01 and false discovery rate [FDR] < 0.05) we have identified 30 circRNA upregulated in colorectal cancer versus non tumour samples. CircRNA/microRNA interaction prediction analysis showed that most upregulated circRNAs contain miRNA Binding Sites (MREs) for cancer-related miRNA, including among others, miR-17, miR-103, miR-let-7g. Conclusions: Microarray analysis was used to comprehensively identify dysregulated circRNAs in CRC. We identify novel circRNAs could be valuable as blood-based CRC biomarkers.


2018 ◽  
Vol 120 (4) ◽  
pp. 6409-6419 ◽  
Author(s):  
Zheying Zhang ◽  
Na Song ◽  
Yongxia Wang ◽  
Jiateng Zhong ◽  
Tengteng Gu ◽  
...  

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.


Author(s):  
Han-Wen Chen ◽  
Xiao-Xia Zhang ◽  
Zhu-Ding Peng ◽  
Zu-Min Xing ◽  
Yi-Wen Zhang ◽  
...  

AbstractTreatment of bone cancer pain (BCP) caused by bone metastasis in advanced cancers remains a challenge in clinical oncology, and the underlying mechanisms of BCP are poorly understood. This study aimed to investigate the pathogenic roles of circular RNAs (circRNAs) in regulating cancer cell proliferation and BCP development. Eight differentially expressed circRNAs in the rat spinal cord were validated by agarose gel electrophoresis and Sanger sequencing. Expression of circRNAs and mRNAs was detected by quantitative RT-PCR. MTS assay and flow cytometry were performed to analyze cell proliferation and apoptosis, respectively. Differentially expressed mRNA profiles were characterized by deep RNA sequencing, hierarchical clustering, and functional categorization. The interactions among circRNAs, microRNAs (miRNAs), and mRNAs were predicted using TargetScan. Additionally, western blot was performed to determine the protein levels of Pax8, Isg15, and Cxcl10. Multiple circRNAs were differentially expressed in the spinal cords of BCP model rats; of these, circSlc7a11 showed the greatest increase in expression. The overexpression of circSlc7a11 significantly promoted cell proliferation and repressed apoptosis of LLC-WRC 256 and UMR-106 cells, whereas circSlc7a11 silencing produced the opposite effects. Altered expression of circSlc7a11 also induced substantial changes in the mRNA expression profiles of LLC-WRC 256 cells; these changes were linked to multiple apoptotic processes and signaling pathways, such as the chemokine signaling pathway, and formed a complex circRNA/miRNA/mRNA network. Additionally, Pax8, Isg15, and Cxc110 protein level in LLC-WRC 256 cells was consistent with the mRNA results. The circRNA circSlc7a11 regulates rat BCP development by modulating LLC-WRC 256 cell proliferation and apoptosis through multiple-signaling mechanisms.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ying Xie ◽  
Xiaofeng Hang ◽  
Wensheng Xu ◽  
Jing Gu ◽  
Yuanjing Zhang ◽  
...  

Abstract Background Most of the biological functions of circular RNAs (circRNAs) and the potential underlying mechanisms in hepatocellular carcinoma (HCC) have not yet been discovered. Methods In this study, using circRNA expression data from HCC tumor tissues and adjacent tissues from the Gene Expression Omnibus database, we identified out differentially expressed circRNAs and verified them by qRT-PCT. Functional experiments were performed to evaluate the effects of circFAM13B in HCC in vitro and in vivo. Results We found that circFAM13B was the most significantly differentially expressed circRNA in HCC tissue. Subsequently, in vitro and in vivo studies also demonstrated that circFAM13B promoted the proliferation of HCC. Further studies revealed that circFAM13B, a sponge of miR-212, is involved in the regulation of E2F5 gene expression by competitively binding to miR-212, inhibits the activation of the P53 signalling pathway, and promotes the proliferation of HCC cells. Conclusions Our findings revealed the mechanism underlying the regulatory role played by circFAM13B, miR-212 and E2F5 in HCC. This study provides a new theoretical basis and novel target for the clinical prevention and treatment of HCC.


Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 921
Author(s):  
Aleksandra Lipka ◽  
Jan Pawel Jastrzebski ◽  
Lukasz Paukszto ◽  
Karol Gustaw Makowczenko ◽  
Elzbieta Lopienska-Biernat ◽  
...  

Impaired fetal growth is one of the most important causes of prematurity, stillbirth and infant mortality. The pathogenesis of idiopathic fetal growth restriction (FGR) is poorly understood but is thought to be multifactorial and comprise a range of genetic causes. This research aimed to investigate non-coding RNAs (lncRNAs) in the placentas of male and female fetuses affected by FGR. RNA-Seq data were analyzed to detect lncRNAs, their potential target genes and circular RNAs (circRNAs); a differential analysis was also performed. The multilevel bioinformatic analysis enabled the detection of 23,137 placental lncRNAs and 4263 of them were classified as novel. In FGR-affected female fetuses’ placentas (ff-FGR), among 19 transcriptionally active regions (TARs), five differentially expressed lncRNAs (DELs) and 12 differentially expressed protein-coding genes (DEGs) were identified. Within 232 differentially expressed TARs identified in male fetuses (mf-FGR), 33 encompassed novel and 176 known lncRNAs, and 52 DEGs were upregulated, while 180 revealed decreased expression. In ff-FGR ACTA2-AS1, lncRNA expression was significantly correlated with five DEGs, and in mf-FGR, 25 TARs were associated with DELs correlated with 157 unique DEGs. Backsplicing circRNA processes were detected in the range of H19 lncRNA, in both ff- and mf-FGR placentas. The performed global lncRNAs characteristics in terms of fetal sex showed dysregulation of DELs, DEGs and circRNAs that may affect fetus growth and pregnancy outcomes. In female placentas, DELs and DEGs were associated mainly with the vasculature, while in male placentas, disturbed expression predominantly affected immune processes.


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