scholarly journals Identification of differentially expressed circular RNAs in human colorectal cancer

Tumor Biology ◽  
2017 ◽  
Vol 39 (3) ◽  
pp. 101042831769454 ◽  
Author(s):  
Peili Zhang ◽  
Zhigui Zuo ◽  
Wenjing Shang ◽  
Aihua Wu ◽  
Ruichun Bi ◽  
...  

Circular RNA, a class of non-coding RNA, is a new group of RNAs and is related to tumorigenesis. Circular RNAs are suggested to be ideal candidate biomarkers with potential diagnostic and therapeutic implications. However, little is known about their expression in human colorectal cancer. In our study, differentially expressed circular RNAs were detected using circular RNA array in paired tumor and adjacent non-tumorous tissues from six colorectal cancer patients. Expression levels of selected circular RNAs (hsa_circRNA_103809 and hsa_circRNA_104700) were measured by real-time polymerase chain reaction in 170 paired colorectal cancer samples for validation. Statistical analyses were conducted to investigate the association between hsa_circRNA_103809 and hsa_circRNA_104700 expression levels and respective patient clinicopathological features. Receiver operating characteristic curve was constructed to evaluate the diagnostic values. Our results indicated that there were 125 downregulated and 76 upregulated circular RNAs in colorectal cancer tissues compared with normal tissues. We also first demonstrated that the expression levels of hsa_circRNA_103809 ( p < 0.0001) and hsa_circRNA_104700 ( p = 0.0003) were significantly lower in colorectal cancer than in normal tissues. The expression level of hsa_circRNA_103809 was significantly correlated with lymph node metastasis ( p = 0.021) and tumor-node-metastasis stage ( p = 0.011), and the expression level of hsa_circRNA_104700 was significantly correlated with distal metastasis ( p = 0.036). The area under receiver operating characteristic curves of hsa_circRNA_103809 and hsa_circRNA_104700 were 0.699 ( p < 0.0001) and 0.616 ( p < 0.0001), respectively. In conclusion, these results suggest that hsa_circRNA_103809 and hsa_circRNA_104700 may be potentially involved in the development of colorectal cancer and serve as potential biomarkers for the diagnosis of colorectal cancer.

2020 ◽  
Author(s):  
Liang Jing ◽  
Junhui Wu ◽  
Xiaocheng Tang ◽  
Min Ma ◽  
Fei Long ◽  
...  

Abstract Background: Circular RNAs (circRNAs) are a novel class of noncoding RNAs. Increasing evidence indicates that circRNAs play an important role in the occurrence and development of tumors. However, the role of circRNA hsa_circ_0044556 in the progression of colorectal cancer (CRC) remains unclear. Methods: First, we searched for differentially expressed circRNAs using a circRNA microarray in paired CRC and adjacent normal tissues. The circRNA hsa_circ_0044556 was screened out from the existing CRC circRNA microarray in the Gene Expression Omnibus database and our microarray. The clinical significance of hsa_circ_0044556 expression level in CRC patients was then investigated. Finally, the functions of the targets of this circRNA were determined in CRC cell lines.Results:Hsa_circ_0044556 was highly expressed in CRC patients and was positively correlated with tumor stage and lymph node metastasis. In CRC cell lines, the proliferation, migration, and invasion of cancer cells were inhibited by knocking down hsa_circ_0044556 expression.Conclusion: Hsa_circ_0044556 promoted the progression of CRC. It is possible that hsa_circ_0044556 will become a novel biomarker or therapeutic target for CRC.


2020 ◽  
Author(s):  
Liang Jing ◽  
Junhui Wu ◽  
Xiaocheng Tang ◽  
Min Ma ◽  
Fei Long ◽  
...  

Abstract Background Circular RNAs (circRNAs) are a novel class of noncoding RNAs. Increasing evidence indicates that circRNAs play an important role in the occurrence and development of tumors. However, the role of circRNAs in the development and progression of colorectal cancer (CRC) remains unclear. Methods First, we searched for differentially expressed circRNAs using a circRNA microarray in paired CRC and adjacent normal tissues. The circRNA hsa_circ_0044556 was screened out from the existing CRC circRNA microarray in the Gene Expression Omnibus database and our microarray. The clinical significance of hsa_circ_0044556 expression level in CRC patients was then investigated. Finally, the functions of the targets of this circRNA were determined in CRC cell lines. Results hsa_circ_0044556 was highly expressed in CRC patients and was positively correlated with tumor stage and lymph node metastasis. In CRC cell lines, the proliferation, migration, and invasion of cancer cells were inhibited by knocking down hsa_circ_0044556 expression. Conclusion hsa_circ_0044556 promoted the development and progression of CRC. It is possible that hsa_circ_0044556 will become a novel biomarker or therapeutic target for CRC.


2020 ◽  
Author(s):  
Liang Jing ◽  
Junhui Wu ◽  
Xiaocheng Tang ◽  
Min Ma ◽  
Fei Long ◽  
...  

Abstract Background: Circular RNAs (circRNAs) are a novel class of noncoding RNAs. Increasing evidence indicates that circRNAs play an important role in the occurrence and development of tumors. However, the role of circRNA hsa_circ_0044556 in the progression of colorectal cancer (CRC) remains unclear. Methods: First, we searched for differentially expressed circRNAs using a circRNA microarray in paired CRC and adjacent normal tissues. The circRNA hsa_circ_0044556 was screened out from the existing CRC circRNA microarray in the Gene Expression Omnibus database and our microarray. The clinical significance of hsa_circ_0044556 expression level in CRC patients was then investigated. Finally, the functions of the targets of this circRNA were determined in CRC cell lines.Results:Hsa_circ_0044556 was highly expressed in CRC patients and was positively correlated with tumor stage and lymph node metastasis. In CRC cell lines, the proliferation, migration, and invasion of cancer cells were inhibited by knocking down hsa_circ_0044556 expression.Conclusion: Hsa_circ_0044556 promoted the progression of CRC. It is possible that hsa_circ_0044556 will become a novel biomarker or therapeutic target for CRC.


2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Fei Pan ◽  
Dongqing Zhang ◽  
Na Li ◽  
Mei Liu

circRNAs (circular RNAs) are a family of noncoding RNAs and have diverse physiological and pathological functions. However, the functions and mechanisms of circRNAs in the development and progression of colorectal cancer (CRC) remain largely unknown. Here, we aimed to explore the functions and roles of circFAT1(e2) in CRC. qRT-PCR revealed that circFAT1(e2) in CRC tumor tissues was upregulated compared with that in adjacent normal tissues and was also upregulated in CRC cell lines. Small interfering RNAs (siRNAs) against circFAT1(e2) were used to decrease the expression of circFAT1(e2) in HCT116 and RKO cells in vitro. The roles of circFAT1(e2) in CRC cell metastasis and proliferation were then determined by transwell and CCK-8 assays. The results showed that circFAT1(e2) silencing markedly suppressed CRC growth. Moreover, we identified circFAT1(e2) as a promoter of CRC metastasis. Knockdown of circFAT1(e2) evidently reduced HCT116 and RKO cell migration and invasion. Furthermore, the regulatory relationship between circFAT1(e2) and its target miRNAs was verified by a luciferase reporter assay. We demonstrated that circFAT1(e2) could sponge miR-30e-5p, which regulated the expression level of integrin α6 (ITGA6), the downstream target gene of miR-30e-5p. Rescue assays demonstrated that knockdown of miR-30e-5p enhanced CRC proliferation and migration via ITGA6. Taken together, our results reveal the novel oncogenic roles of circFAT1(e2) in CRC through the miR-30e-5p/ITGA6 axis.


2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Melika Ameli-Mojarad ◽  
Mandana Ameli-Mojarad ◽  
Mitra Nourbakhsh ◽  
Ehsan Nazemalhosseini-Mojarad

Breast cancer (BC) is one of the most common lethal diseases in women worldwide. Recent evidence has shown that covalently closed Circular RNA (circRNA) deregulation is observed in different human malignancies and cancers. Lately, circRNAs are being considered as a new diagnostic biomarker; however, the mechanism and the correlation of action between circRNAs and BC are still unclear. In the present study, we try to investigate the expression level of hsa_circ_0005046 and hsa_circ_0001791 in BC. By using quantitative real-time polymerase chain reaction (qRT-PCR), expression profiles of candidate circRNAs were detected in 60 BC tissue and paired adjacent normal tissues. Furthermore, the clinicopathological relation and diagnostic value were estimated. Our results showed the higher expression levels of hsa_circ_0005046 and hsa_circ_0001791 in BC tissues compared to paired adjacent normal tissues with P value ( P < 0.0001 ) for both circRNAs, and the area under the receiver operating characteristic (ROC) curve was 0.857 and 1.0, respectively; in addition, a total 10 miRNAs that can be targeted by each candidate circRNAs was predicted base on bioinformatics databases. Taken together, for the first time, the results of our study presented high expression levels of hsa_circ_0005046 and hsa_circ_00017916 in BC; although there was no direct correlation between the high expression level of both circRNAs with clinic pathological factors, except hsa_circ_0001791 association with estrogen receptors (ER), high ROC curve in expressed samples indicated that both circRNAs could be used as a new diagnostic biomarker for BC. Moreover, miRNAs selection tools predicted that miR-215 and mir-383-5p which have a tumor suppressor role in BC can be targeted by our candidate circRNAs to affect the PI3K/AKT pathway; in conclusion, further studies are required to validate the oncogene role of our candidate circRNAs through the PI3k pathway.


2016 ◽  
Vol 24 (4) ◽  
pp. 369-375
Author(s):  
Liu Bin ◽  
Meng Zhang ◽  
Liu Lixia ◽  
Zang Aimin ◽  
Yang Hua ◽  
...  

Abstract Background: MiRNA-30c was a tumor suppressor in several human cancers, however, its association with clinicopathological features and prognosis in colorectal cancer (CRC) is unclear. Materials and Methods: The expression level of miRNA-30c in 192 pairs of colorectal cancer and adjacent normal tissues was detected by Quantitative RT-PCR, the association between miRNA-30c expression and clinical characteristics and prognosis were statistically analyzed. Results: miRNA-30c was significantly lower in CRC tissues specimens compared with matched normal adjacent tissue (P<0.001). MiRNA-30c was positively correlated with tumor size (P=0.012), TMN stage (P=0.002) and lymph node metastasis (P=0.004). The univariate analysis showed CRC patients with low miRNA-30c had distinctly shorter overall survival (P<0.001) than patients with high miRNA-30c expression level. The multivariate analysis was performed and informed that low miRNA-30c expression (P<0.001) might be an independent prognostic predictor for poor prognosis. Conclusion: miRNA-30c could predict the prognosis of colorectal cancer which is helpful to choose reasonable treatment measures.


2020 ◽  
Author(s):  
Dongxue Lu ◽  
Jing Yan ◽  
Zhiguang Sun ◽  
Xuan Li ◽  
Feng Liu ◽  
...  

Abstract BackgroundColorectal cancer is the life-threatening tumor with both high prevalence and mortality worldwide. However, the molecular mechanism behind it remains unknown. Methods: Herein, the potential prognostic candidate biomarkers for colorectal cancer were tested by Bioinformatical analysis combined with the CRC clinical samples. Three data sets (GSE32323, GSE44076 and GSE43078) were collected from the gene expression omnibus (GEO). The limma and clusterProfifiler packages were used to identify differentially expressed genes (DEGs) and conduct functional enrichment analysis, respectively. To retrieve Interacting Genes (STRING) database, protein–protein interaction (PPI) network was built up using Search Tool, and Cytoscape was applied to carry out the module analysis. Subsequently, the online tool GEPIA was employed to conduct overall survival analysis (http://gepia.cancer-pku.cn/index.html), and the Oncomine database was used to analyze prognostic candidate biomarkers. Finally, 4 key hub genes were selected for validation of their expression levels in 9 patients newly diagnosed with CRC via reverse transcription‑quantitative PCR (RT‑qPCR). To evaluate the accuracy of prediction, time-dependent receiver operating characteristic (ROC) was applied.ResultsIn total, 547 DEGs got identifified, inclusive of 475 downregulated and 72 upregulated genes with a signifificant enrichment in the cellular response to hypoxia, the positive control of ERK1 and ERK2 cascade and the positive control of apoptotic process. The enhanced pathways were Pathways in cancer,PI3K-Akt signaling pathway,cGMP-PKG signaling pathway. Through the extraction of critical modules from the PPI network, 10 hub genes got removed. These 10 hub genes are all up-regulated genes and are highly expressed in colorectal cancer. Survival analysis shows that only CCNB1 and CCNA2 are associated with the survival prediction of colorectal cancer. Moreover, consistence is show between the TCGA data sets and the expression levels of the 4 hub genes. Receiver Operating Characteristic(ROC) curves showed that all CCNB1,CCNA2,AURKA and BUB1B have potential predictive value.Briely, new hub genes identifified can shed light on the underlying mechanism behind CRC carcinogenesis and development, which is coducive to detecting and treating CRC timely.


Author(s):  
Marzieh Ghani Dehkordi ◽  
Maryam Peymani

Introduction: In recent studies, methylation of FOXE1 in colorectal cancer has been reported as a diagnostic biomarker. In this study for the first time, the expression of FOXE1 and PTCSC2 in colorectal cancer was investigated and their expression patterns in two healthy and tumor tissues of patients were compared. Methods: In this study, 40 tumor tissues with colorectal cancer and 40 adjacent normal samples were collected. Total RNA was extracted and cDNA synthesis followed. Then, the specific genes for lncRNA PTCSC2 and FOXE1 were amplified. The results were statistically analyzed by Graph Pad Prism software and a T-test was used to compare the expression levels of lncRNA PTCSC2 and FOXE1 in the patients and healthy group; p-value less than 0.05 was considered significant difference criteria. Results: In this study, the FOXE1 expression level was significantly decreased in tumor tissue (p-value = 0.005), whereas the lncRNA PTCSC2 expression level in tumor tissue was not significantly changed (p-value = 0.65). In addition, the expression levels of FOXE1 and lncRNA PTCSC2 did not show a significant relation with disease progression and age of the patients. ROC curve for changes in FOXE1 and lncRNA PTCSC2 expression showed that theFOXE1 gene could be a relatively appropriate independent variable (p-value = 0.03) to differentiate between the two study groups. Conclusion: According to the results of this study, changes in FOXE1 gene expression were significantly reduced in tumor samples and can be used as a biomarker in tumor diagnosis in colorectal cancer.


2021 ◽  
Author(s):  
Zhi-Lei Chen ◽  
Hong-Yu Chen ◽  
Lei Yang ◽  
Xiang-Nan Li ◽  
Zhenjun Wang

Abstract Background: Studies have demonstrated that circular RNAs (circRNAs) play important roles in various types of cancer; however, the mechanisms of circRNAs located in the nucleus have rarely been explored. Here, we reported a novel circular RNA circPLCE1 facilitates the malignant progression of colorectal cancer (CRC) via repression of SRSF2-dependent PLCE1 pre-RNA splicing. Methods: qRT-PCR was used to determine the expression of circPLCE1 in CRC tissues and cells. CCK-8, transwell and flow cytometric assays were used to assess the role of circPLCE1 in CRC cell proliferation, migration and apoptosis, respectively. Animal study was carried to test the role of circPLCE1 in vivo. Further, catRAPID and RPISeq were applied to predict the possible binding protein of circPLCE1. RNA fractionation and RIP assays were used to confirm the RNA-protein interaction. Results: In this study, we found that circPLCE1 was significantly downregulated in CRC tissues compared with adjacent normal tissues. However, circPLCE1 knockdown suppresses CRC cell proliferation, migration, invasion and increased apoptosis. Nude mice experiments showed that ectopic expression of circPLCE1 dramatically increased tumor growth in vivo. Mechanically, circPLCE1 directly binding to SRSF2 protein, repressing SRSF2-dependent PLCE1 pre-RNA splicing, resulting in the progression of CRC. Individually mutating the binding sites of circPLCE1 derepressed the production of PLCE1 mRNA. Conclusions: Our studies revealed a novel molecular mechanism in the regulation of PLCE1 and implicated a new function of circular RNA, supporting the pursuit of circPLCE1 as a potential tool for future CRC treatment.


2021 ◽  
Vol 11 (2) ◽  
pp. 126
Author(s):  
Noshad Peyravian ◽  
Stefania Nobili ◽  
Zahra Pezeshkian ◽  
Meysam Olfatifar ◽  
Afshin Moradi ◽  
...  

This study aimed at building a prognostic signature based on a candidate gene panel whose expression may be associated with lymph node metastasis (LNM), thus potentially able to predict colorectal cancer (CRC) progression and patient survival. The mRNA expression levels of 20 candidate genes were evaluated by RT-qPCR in cancer and normal mucosa formalin-fixed paraffin-embedded (FFPE) tissues of CRC patients. Receiver operating characteristic curves were used to evaluate the prognosis performance of our model by calculating the area under the curve (AUC) values corresponding to stage and metastasis. A total of 100 FFPE primary tumor tissues from stage I–IV CRC patients were collected and analyzed. Among the 20 candidate genes we studied, only the expression levels of VANGL1 significantly varied between patients with and without LNMs (p = 0.02). Additionally, the AUC value of the 20-gene panel was found to have the highest predictive performance (i.e., AUC = 79.84%) for LNMs compared with that of two subpanels including 5 and 10 genes. According to our results, VANGL1 gene expression levels are able to estimate LNMs in different stages of CRC. After a proper validation in a wider case series, the evaluation of VANGL1 gene expression and that of the 20-gene panel signature could help in the future in the prediction of CRC progression.


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