This preprint is under consideration at Cancer Cell International. A preprint is 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.
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Primary research
Lu Wang
Fudan University Shanghai Cancer Center
Corresponding Author
ORCiD: https://orcid.org/0000-0001-8656-2183
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
Interferon-alpha (IFN-α) is a general therapeutic regimen to be utilized in HCC. However, regulatory mechanisms of IFN-α on competing endogenous RNAs (ceRNAs) level in HCC are rarely understood.
Methods
HCC patients with and without IFN-α treatment were calculated to analyze the expression profile of mRNA, lncRNA, miRNA, and circRNA by RNA sequence, and significant differential expression (DE) of these types of RNAs were screened out for the following analysis. A ceRNA regulatory network was constructed to explore effects of IFN-α intervention on HCC. Furthermore, the potential prognostic factors among these DE RNAs were identified.
Results
In total, 60 (0.37%) mRNAs, 23 (0.08%) circRNAs, 15 (0.11%) lncRNAs, and 23 (0.91%) miRNAs were differentially expressed in patients who received IFN-α treatment. A ceRNA regulatory network including a circRNA-miRNA-mRNA network which composed of 4 up- and 10 down-regulated circRNAs, 8 up- and 5 down-regulated miRNAs, 28 up- and 9 down-regulated mRNAs, and a lncRNA-miRNA-mRNA network which composed of 10 up- and 3 down-regulated lncRNAs, 11 up- and 5 down-regulated miRNAs, 28 up- and 10 down-regulated mRNAs was constructed. Gene enrichment and pathway analysis revealed that the ceRNA network was associated with immune-related pathway and corresponding molecular function in patients who accepted IFN-α treatment. Next, we identified 3 most relevant to IFN-α treatment to HCC among these DE RNAs, namely FAM20A,IGFBP4 and MARCH3, as the prognostic factors of HCC. Furthermore, MARCH3 expression was positively correlated with infiltrating levels of CD4 + T and CD8 + T cells, macrophages, neutrophils, and dendritic cells (DCs) in HCC. MARCH3 expression showed strong correlations with diverse immune marker sets in HCC.
Conclusion
Our data discovered a novel ceRNA network in HCC patients receiving IFN-α therapy, which might lay the foundation for better understand the regulatory mechanism of IFN-α treatment.
Keywords
Hepatocellular carcinoma, Interferon-alpha, RNA sequencing, Competing endogenous RNAs, MARCH3, Tumor-infiltrating
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CURRENT STATUS: Under Review
Version (no preprint)
Posted 17 Jul, 2021
Reviews received
Received 17 Jul, 2021
Reviewers invited
Invitations sent on 17 Jul, 2021
Editor assigned
On 09 Jul, 2021
First submitted
On 09 Jul, 2021
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Version (no preprint)
Posted 10 Jul, 2021
This version was not preprinted
Version (no preprint)
Posted 08 Jun, 2021
Editorial decision: Major revision
On 08 Jun, 2021
Review #4 received
Received 06 Jun, 2021
Review #3 received
Received 25 May, 2021
Reviewer #4 agreed
On 24 May, 2021
Reviewer #3 agreed
On 24 May, 2021
Review #1 received
Received 24 May, 2021
Reviewer #2 agreed
On 23 May, 2021
Review #2 received
Received 23 May, 2021
Reviews received
Received 22 May, 2021
Reviewer #1 agreed
On 22 May, 2021
Reviewers invited
Invitations sent on 22 May, 2021
Editor assigned
On 18 May, 2021
Submission checks complete
On 17 May, 2021
Editor invited
On 17 May, 2021
First submitted
On 17 May, 2021
This version was not preprinted
Version (no preprint)
Posted 25 May, 2021
This version was not preprinted
Version (no preprint)
Posted 17 May, 2021
Editor assigned
On 17 May, 2021
Submission checks complete
On 17 May, 2021
Editor invited
On 17 May, 2021
This version was not preprinted
Version 1
Posted 18 Mar, 2021
No community comments so far
Editorial decision: Major revision
On 18 Apr, 2021
Review #4 received
Received 16 Apr, 2021
Review #3 received
Received 14 Apr, 2021
Review #1 received
Received 06 Apr, 2021
Review #2 received
Received 06 Apr, 2021
Reviewer #5 agreed
On 05 Apr, 2021
Reviewer #4 agreed
On 04 Apr, 2021
Reviewer #3 agreed
On 04 Apr, 2021
Reviewer #2 agreed
On 03 Apr, 2021
Reviewer #1 agreed
On 03 Apr, 2021
Reviews received
Received 03 Apr, 2021
Reviewers invited
Invitations sent on 02 Apr, 2021
Editor assigned
On 16 Mar, 2021
Submission checks complete
On 16 Mar, 2021
Editor invited
On 16 Mar, 2021
First submitted
On 18 Feb, 2021
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Cancer Biology
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This preprint is under consideration at Cancer Cell International. A preprint is 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
Lu Wang
Fudan University Shanghai Cancer Center
Corresponding Author
ORCiD: https://orcid.org/0000-0001-8656-2183
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
Version (no preprint)
Posted 17 Jul, 2021
Reviews received
Received 17 Jul, 2021
Reviewers invited
Invitations sent on 17 Jul, 2021
Editor assigned
On 09 Jul, 2021
First submitted
On 09 Jul, 2021
This version was not preprinted
Version (no preprint)
Posted 10 Jul, 2021
This version was not preprinted
Version (no preprint)
Posted 08 Jun, 2021
Editorial decision: Major revision
On 08 Jun, 2021
Review #4 received
Received 06 Jun, 2021
Review #3 received
Received 25 May, 2021
Reviewer #4 agreed
On 24 May, 2021
Reviewer #3 agreed
On 24 May, 2021
Review #1 received
Received 24 May, 2021
Reviewer #2 agreed
On 23 May, 2021
Review #2 received
Received 23 May, 2021
Reviews received
Received 22 May, 2021
Reviewer #1 agreed
On 22 May, 2021
Reviewers invited
Invitations sent on 22 May, 2021
Editor assigned
On 18 May, 2021
Submission checks complete
On 17 May, 2021
Editor invited
On 17 May, 2021
First submitted
On 17 May, 2021
This version was not preprinted
Version (no preprint)
Posted 25 May, 2021
This version was not preprinted
Version (no preprint)
Posted 17 May, 2021
Editor assigned
On 17 May, 2021
Submission checks complete
On 17 May, 2021
Editor invited
On 17 May, 2021
This version was not preprinted
Version 1
Posted 18 Mar, 2021
No community comments so far
Editorial decision: Major revision
On 18 Apr, 2021
Review #4 received
Received 16 Apr, 2021
Review #3 received
Received 14 Apr, 2021
Review #1 received
Received 06 Apr, 2021
Review #2 received
Received 06 Apr, 2021
Reviewer #5 agreed
On 05 Apr, 2021
Reviewer #4 agreed
On 04 Apr, 2021
Reviewer #3 agreed
On 04 Apr, 2021
Reviewer #2 agreed
On 03 Apr, 2021
Reviewer #1 agreed
On 03 Apr, 2021
Reviews received
Received 03 Apr, 2021
Reviewers invited
Invitations sent on 02 Apr, 2021
Editor assigned
On 16 Mar, 2021
Submission checks complete
On 16 Mar, 2021
Editor invited
On 16 Mar, 2021
First submitted
On 18 Feb, 2021
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
Background
Interferon-alpha (IFN-α) is a general therapeutic regimen to be utilized in HCC. However, regulatory mechanisms of IFN-α on competing endogenous RNAs (ceRNAs) level in HCC are rarely understood.
Methods
HCC patients with and without IFN-α treatment were calculated to analyze the expression profile of mRNA, lncRNA, miRNA, and circRNA by RNA sequence, and significant differential expression (DE) of these types of RNAs were screened out for the following analysis. A ceRNA regulatory network was constructed to explore effects of IFN-α intervention on HCC. Furthermore, the potential prognostic factors among these DE RNAs were identified.
Results
In total, 60 (0.37%) mRNAs, 23 (0.08%) circRNAs, 15 (0.11%) lncRNAs, and 23 (0.91%) miRNAs were differentially expressed in patients who received IFN-α treatment. A ceRNA regulatory network including a circRNA-miRNA-mRNA network which composed of 4 up- and 10 down-regulated circRNAs, 8 up- and 5 down-regulated miRNAs, 28 up- and 9 down-regulated mRNAs, and a lncRNA-miRNA-mRNA network which composed of 10 up- and 3 down-regulated lncRNAs, 11 up- and 5 down-regulated miRNAs, 28 up- and 10 down-regulated mRNAs was constructed. Gene enrichment and pathway analysis revealed that the ceRNA network was associated with immune-related pathway and corresponding molecular function in patients who accepted IFN-α treatment. Next, we identified 3 most relevant to IFN-α treatment to HCC among these DE RNAs, namely FAM20A,IGFBP4 and MARCH3, as the prognostic factors of HCC. Furthermore, MARCH3 expression was positively correlated with infiltrating levels of CD4 + T and CD8 + T cells, macrophages, neutrophils, and dendritic cells (DCs) in HCC. MARCH3 expression showed strong correlations with diverse immune marker sets in HCC.
Conclusion
Our data discovered a novel ceRNA network in HCC patients receiving IFN-α therapy, which might lay the foundation for better understand the regulatory mechanism of IFN-α treatment.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
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