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.
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.
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.
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.
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Posted 18 Mar, 2021
Received 06 Apr, 2021
On 05 Apr, 2021
On 04 Apr, 2021
On 04 Apr, 2021
On 03 Apr, 2021
On 03 Apr, 2021
Received 03 Apr, 2021
Invitations sent on 02 Apr, 2021
On 16 Mar, 2021
On 16 Mar, 2021
On 16 Mar, 2021
On 18 Feb, 2021
Posted 18 Mar, 2021
Received 06 Apr, 2021
On 05 Apr, 2021
On 04 Apr, 2021
On 04 Apr, 2021
On 03 Apr, 2021
On 03 Apr, 2021
Received 03 Apr, 2021
Invitations sent on 02 Apr, 2021
On 16 Mar, 2021
On 16 Mar, 2021
On 16 Mar, 2021
On 18 Feb, 2021
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.
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.
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.
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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