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. 2021 Jun 16;13(12):16124-16143.
doi: 10.18632/aging.203139. Epub 2021 Jun 16.

Identification of RNA binding protein interacting with circular RNA and hub candidate network for hepatocellular carcinoma

Binglin Cheng  1 , Jingdong Tian  2 , Yuhan Chen  3
Affiliations

Identification of RNA binding protein interacting with circular RNA and hub candidate network for hepatocellular carcinoma

Binglin Cheng et al. Aging (Albany NY). .

Abstract

The interaction between RNA binding protein (RBP) and circular RNA (circRNA) is important for the regulation of tumor progression. This study aimed to identify the RBP-circRNA network in hepatocellular carcinoma (HCC). 22 differentially expressed (DE) circRNAs in HCC were screened out from Gene Expression Omnibus (GEO) database and their binding RBPs were predicted by Circular RNA Interactome. Among them, 17 DERBPs, which were commonly dysregulated in HCC from The Clinical Proteomic Tumor Analysis Consortium (CPTAC), The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) projects, were utilized to construct the RBP-circRNA network. Through survival analysis, we found TARDBP was the only prognostic RBP for HCC in CPTAC, TCGA and ICGC projects. High expression of TARDBP was correlated with high grade, advanced stage and low macrophage infiltration of HCC. Additionally, gene set enrichment analysis showed that dysregulated TARDBP might be involved in some pathways related to the HCC pathogenesis. Therefore, a hub RBP-circRNA network was generated based on TARDBP. RNA immunoprecipitation and RNA pull-down confirmed that hsa_circ_0004913 binds to TARDBP. These findings indicated certain RBP-circRNA regulatory network potentially involved in the pathogenesis of HCC, which provides novel insights into the mechanism study and biomarker identification for HCC.

Keywords: RNA binding protein; circular RNA; hepatocellular carcinoma; regulatory network.

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Conflict of interest statement

CONFLICTS OF INTEREST: The authors declare no conflicts of interest related to this study.

Figures

Figure 1
Figure 1
The expression of RBPs in non-tumor and HCC cases from CPTAC (A), TCGA (B) and ICGC (C) projects.
Figure 2
Figure 2
Construction of the RBP-circRNA regulatory network in HCC.
Figure 3
Figure 3
Prognostic value and clinicopathologic characteristics correlation of TARDBP in HCC. (A) Survival analysis of TARDBP in HCC from CPTAC, TCGA and ICGC projects. (B–D) Comparison of TARDBP expression level between different clinicopathologic characteristics in CPTAC (B), TCGA (C) and ICGC (D) projects.
Figure 4
Figure 4
Prognostic analysis of TARDBP and other clinicopathological traits for HCC from CPTAC (A), TCGA (B) and ICGC (C) projects by Cox regression.
Figure 5
Figure 5
GSEA of HCC cases with TARDBP low- and high-expression in TCGA (A) or ICGC (B) projects.
Figure 6
Figure 6
Immune cell fractions of HCC cases with TARDBP low- and high-expression from TCGA (A) and ICGC (B) projects.
Figure 7
Figure 7
Analysis of TARDBP- hsa_circ_0004913 network in HCC. (A) The immunohistochemistry staining of TARDBP in normal and HCC tissues from HPA. (B) qRT-PCR analysis of hsa_circ_0004913 in MIHA (normal hepatocyte) and HCC cells. P < 0.05 vs. MIHA cell. (C) RIP analysis of hsa_circ_0004913 enriched in TARDBP IP samples compared with IgG samples. P < 0.05 vs. IgG samples. (D) RNA pull-down analysis of the binding ability of hsa_circ_0004913 for TARDBP.
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