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Background: Colorectal cancer (CRC) is a common malignant tumor with unsatisfactory overall prognosis. CircRNAs could be promising prognostic biomarkers in cancers, and play important role in the process of tumorigenesis and progression. Here, we explored the role of hsa_circ_0004831 in blood extracellular vesicles and its prognostic value in CRC.
Methods: The circRNA and mRNA expression level matrix in extracellular vesicles of CRC and normal samples were obtained from the exoRBase database. The corresponding miRNA expression level matrix in extracellular vesicles was downloaded from the BBCancer database. Differentially expressed circRNAs, miRNAs and mRNAs were identified using the limma package of R software at the cut-off criteria of fold change (FC) > 2 and adj. p < 0.05. RT-qPCR assay was conducted to measure hsa_circ_0004831 expression level in CRC blood samples. A circRNA-miRNA-mRNA regulatory network of hsa_circ_0004831 was constructed based on competitive endogenous RNA mechanism and differentially expressed genes. The mRNAs co-expressed with hsa_circ_0004831 were screened at the cut-off criteria of pearson |r| > 0.3 and p < 0.05. Gene set enrichment analysis (GSEA) based on co-expressed mRNAs was used to explore the potential molecular function of hsa_circ_0004831.
Results: Differentially expressed circRNAs, miRNAs and mRNAs were identified and hsa_circ_0004831 had a FC value of 3.92 in CRC blood extracellular vesicles. The RT-qPCR assay showed that the hsa_circ_0004831 was up-regulated in CRC blood samples. The overall survival analysis found that high expression of hsa_circ_0004831 was linked with poorer prognosis. Finally, a circRNA-miRNA-mRNA regulatory network of hsa_circ_0004831 was constructed based on down-regulated miR-4326 and 12 up-regulated mRNAs. GSEA indicated that mRNAs co-expressed with hsa_circ_0004831 were involved in EMT, WNT and p53 signaling pathways.
Conclusions: The study confirmed the up-regulation of hsa_circ_0004831 in CRC, and it may act as a vital prognostic biomarker. The circRNA-miRNA-mRNA regulatory network of hsa_circ_0004831 could be used to uncover the tumorigenesis and progression of CRC.
Keywords
Colorectal cancer, CircRNA, Extracellular vesicle, Competitive endogenous RNA, Prognosis
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CURRENT STATUS: Published
View the published article at Cancer Cell International.
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Posted 27 Oct, 2020
No community comments so far
Editorial decision: Accept
On 07 Nov, 2020
Reviewer #2 agreed
On 01 Nov, 2020
Review #2 received
Received 01 Nov, 2020
Review #1 received
Received 01 Nov, 2020
Reviewers invited
Invitations sent on 31 Oct, 2020
Reviewer #1 agreed
On 31 Oct, 2020
Editor assigned
On 20 Oct, 2020
Submission checks complete
On 19 Oct, 2020
Editor invited
On 19 Oct, 2020
No comments provided
Reviewers invited
Invitations sent on 13 Oct, 2020
Reviewer #1 agreed
On 13 Oct, 2020
Reviewer #2 agreed
On 13 Oct, 2020
Review #1 received
Received 13 Oct, 2020
Editor assigned
On 28 Sep, 2020
Submission checks complete
On 27 Sep, 2020
Editor invited
On 27 Sep, 2020
No comments provided
Reviewer #2 agreed
On 07 Sep, 2020
Review #2 received
Received 07 Sep, 2020
Editorial decision: Major revision
On 07 Sep, 2020
Review #1 received
Received 02 Sep, 2020
Reviewer #1 agreed
On 19 Aug, 2020
Reviewers invited
Invitations sent on 18 Aug, 2020
Editor assigned
On 10 Aug, 2020
Submission checks complete
On 09 Aug, 2020
Editor invited
On 09 Aug, 2020
First submitted
On 06 Aug, 2020
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Cancer Biology
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See the published version of this preprint at Cancer Cell International.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Primary research
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Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
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Peer Review Timeline
CURRENT STATUS: Published
View the published article at Cancer Cell International.
Version 3
Posted 27 Oct, 2020
No community comments so far
Editorial decision: Accept
On 07 Nov, 2020
Reviewer #2 agreed
On 01 Nov, 2020
Review #2 received
Received 01 Nov, 2020
Review #1 received
Received 01 Nov, 2020
Reviewers invited
Invitations sent on 31 Oct, 2020
Reviewer #1 agreed
On 31 Oct, 2020
Editor assigned
On 20 Oct, 2020
Submission checks complete
On 19 Oct, 2020
Editor invited
On 19 Oct, 2020
No comments provided
Reviewers invited
Invitations sent on 13 Oct, 2020
Reviewer #1 agreed
On 13 Oct, 2020
Reviewer #2 agreed
On 13 Oct, 2020
Review #1 received
Received 13 Oct, 2020
Editor assigned
On 28 Sep, 2020
Submission checks complete
On 27 Sep, 2020
Editor invited
On 27 Sep, 2020
No comments provided
Reviewer #2 agreed
On 07 Sep, 2020
Review #2 received
Received 07 Sep, 2020
Editorial decision: Major revision
On 07 Sep, 2020
Review #1 received
Received 02 Sep, 2020
Reviewer #1 agreed
On 19 Aug, 2020
Reviewers invited
Invitations sent on 18 Aug, 2020
Editor assigned
On 10 Aug, 2020
Submission checks complete
On 09 Aug, 2020
Editor invited
On 09 Aug, 2020
First submitted
On 06 Aug, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Cancer Biology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Cancer Cell International.
Background: Colorectal cancer (CRC) is a common malignant tumor with unsatisfactory overall prognosis. CircRNAs could be promising prognostic biomarkers in cancers, and play important role in the process of tumorigenesis and progression. Here, we explored the role of hsa_circ_0004831 in blood extracellular vesicles and its prognostic value in CRC.
Methods: The circRNA and mRNA expression level matrix in extracellular vesicles of CRC and normal samples were obtained from the exoRBase database. The corresponding miRNA expression level matrix in extracellular vesicles was downloaded from the BBCancer database. Differentially expressed circRNAs, miRNAs and mRNAs were identified using the limma package of R software at the cut-off criteria of fold change (FC) > 2 and adj. p < 0.05. RT-qPCR assay was conducted to measure hsa_circ_0004831 expression level in CRC blood samples. A circRNA-miRNA-mRNA regulatory network of hsa_circ_0004831 was constructed based on competitive endogenous RNA mechanism and differentially expressed genes. The mRNAs co-expressed with hsa_circ_0004831 were screened at the cut-off criteria of pearson |r| > 0.3 and p < 0.05. Gene set enrichment analysis (GSEA) based on co-expressed mRNAs was used to explore the potential molecular function of hsa_circ_0004831.
Results: Differentially expressed circRNAs, miRNAs and mRNAs were identified and hsa_circ_0004831 had a FC value of 3.92 in CRC blood extracellular vesicles. The RT-qPCR assay showed that the hsa_circ_0004831 was up-regulated in CRC blood samples. The overall survival analysis found that high expression of hsa_circ_0004831 was linked with poorer prognosis. Finally, a circRNA-miRNA-mRNA regulatory network of hsa_circ_0004831 was constructed based on down-regulated miR-4326 and 12 up-regulated mRNAs. GSEA indicated that mRNAs co-expressed with hsa_circ_0004831 were involved in EMT, WNT and p53 signaling pathways.
Conclusions: The study confirmed the up-regulation of hsa_circ_0004831 in CRC, and it may act as a vital prognostic biomarker. The circRNA-miRNA-mRNA regulatory network of hsa_circ_0004831 could be used to uncover the tumorigenesis and progression of CRC.
Figure 1
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