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Aging-US: Hub candidate network for hepatocellular carcinoma

07-25-2021

Aging-US published "Identification of RNA binding protein interacting with circular RNA and hub candidate network for hepatocellular carcinoma" which reported that 17 DERBPs, which were commonly dysregulated in HCC from The Clinical Proteomic Tumor Analysis Consortium, The Cancer Genome Atlas and International Cancer Genome Consortium projects, were utilized to construct the RBP-circRNA network.

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, published in Aging-US, indicated a certain RBP-circRNA regulatory network potentially involved in the pathogenesis of HCC, which provides novel insights into the mechanism of study and biomarker identification for HCC.

These findings, published in Aging-US, indicated a certain RBP-circRNA regulatory network potentially involved in the pathogenesis of HCC, which provides novel insights into the mechanism of study and biomarker identification for HCC.

Dr. Yuhan Chen from The Southern Medical University said, "Hepatocellular carcinoma (HCC) is most common types of primary liver cancer."

Previous studies have demonstrated that circRNAs can act as sponges of RNA binding protein, in the meantime RBPs are also able to participate in back-splicing. Therefore, the interaction with RBPs can be also regarded as a crucial element to explore functions of circRNAs.

However, there are very few studies related to the effects of RBP-circRNA interactions on HCC, which requires more exploration.

In this study, the authors screened out the differently expressed circRNA in HCC cases from Gene Expression Omnibus database and predicted the RBPs binding to DEcircRNA.

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.

After evaluating the expression level of RBPs in HCC from The Clinical Proteomic Tumor Analysis Consortium, International Cancer Genome Consortium and The Cancer Genome Atlas projects, they utilized 17 common DERBPs to construct the RBP-circRNA regulatory network in HCC.

These findings indicated that certain RBP-circRNA networks may be closely related to HCC, which provides ideas for the mechanism of study for HCC.

The Chen Research Team concluded in their Aging-US Research Output, "we identified some DERBPs interacting with circRNAs and generated RBP-circRNA regulatory networks for HCC. Among the DERBPs, high TARDBP expression was corelated with high grade, advanced stage and low macrophage fraction of HCC. We also constructed the hub RBP-circRNA network based on TARDBP and confirmed that hsa_circ_0004913 could bind to TARDBP, which may provide new clues for HCC mechanism study. However, there are also some limitations in our study. First, we only used TCGA, ICGC and CPTAC projects for analysis and little data resulted in only one RBP with prognostic significance, which may lead to the loss of some potential functional RBPs. Second, we didn’t classify samples according to the etiology and these identified circRNAs and RBPs may not be representative in HCC with different etiologies. Moreover, the number of HCC cases with circRNA data included in this study is relatively small. Due to our current lack of HCC samples and no survival information of HCC with circRNA expression profiles in GEO, we could not verify the expression and assess the prognostic value of circRNAs for HCC. In summary, our results indicated that some RBP-circRNA networks take a potential part in the pathogenesis of HCC and provide a new perspective for further mechanism study and biomarker development of HCC."

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DOI - https://doi.org/10.18632/aging.203139

Full Text - https://www.aging-us.com/article/203139/text

Correspondence to: Yuhan Chen email: cspnr1@126.com

Keywords: hepatocellular carcinoma, autophagy, progression, miR-513b-5p, PIK3R3

About Aging-US:

The mission of the journal is to understand the mechanisms surrounding aging and age-related diseases, including cancer as the main cause of death in the modern aged population.

The journal aims to promote 1) treatment of age-related diseases by slowing down aging, 2) validation of anti-aging drugs by treating age-related diseases, and 3) prevention of cancer by inhibiting aging. (Cancer and COVID-19 are age-related diseases.)

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