Multiple Omics Integration Reveals Key Circular RNAs in Hepatocellular Carcinoma
BackgroundHCC is one of the most common malignancies with an increasing incidence worldwide, especially in Asian countries. However, even though targeted cancer therapy drugs such as sorafenib and regorafenib are available, the overall outcome of HCC remains unsatisfactory. Thus, it is urgent to inv...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-05-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.621353/full |
| _version_ | 1819085973388001280 |
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| author | Zi-Li Huang Zi-Li Huang Xiu-Yan Huang Jin Huang Xin-Yu Huang Yong-Hua Xu Jian Zhou Zhao-You Tang |
| author_facet | Zi-Li Huang Zi-Li Huang Xiu-Yan Huang Jin Huang Xin-Yu Huang Yong-Hua Xu Jian Zhou Zhao-You Tang |
| author_sort | Zi-Li Huang |
| collection | DOAJ |
| description | BackgroundHCC is one of the most common malignancies with an increasing incidence worldwide, especially in Asian countries. However, even though targeted cancer therapy drugs such as sorafenib and regorafenib are available, the overall outcome of HCC remains unsatisfactory. Thus, it is urgent to investigate the molecular mechanisms of HCC progression, so as to provide accurate diagnostic criteria and therapeutic targets.MethodsRNA-seq data was used to identify and quantify circular RNAs (circRNAs). DESeq2 was used to identify the differentially expressed circRNAs. miRNA binding sites within circRNAs were identified by miRanda. Gene set enrichment analysis (GSEA) was conducted to predict the biological function of circRNAs.ResultsThe differential expression analysis identified 107 upregulated and 95 downregulated circRNAs in HCC tissues. We observed that a differentially expressed circRNA (DE-circRNA), hsa_circ_0141900 was highly negatively correlated with its parental gene RAB1A (PCC < -0.6), which was also closely associated with mTOR signaling pathway. Moreover, we also constructed competing endogenous RNA (ceRNA) network to identify key circRNAs involved in HCC. Notably, hsa_circ_0002130 and hsa_circ_0008774 were highly correlated with the genes involved in gluconeogenesis and HNF3A pathway via the target genes, GOT2 and AR, suggesting that the two circRNAs might regulate these pathways, respectively. Survival analysis revealed that GOT2 was associated with favorable prognosis. Furthermore, high expression of hsa_circ_0002130 was found to inhibit tumor cell growth and promotes GOT2 expression.ConclusionIn summary, the circRNAs highlighted by the integrative analysis greatly improved our understanding of the underlying mechanism of circRNAs in HCC. |
| first_indexed | 2024-12-21T21:12:52Z |
| format | Article |
| id | doaj.art-a1cf50e443cb44c38916150f63aec197 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-21T21:12:52Z |
| publishDate | 2021-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-a1cf50e443cb44c38916150f63aec1972022-12-21T18:50:05ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-05-011110.3389/fonc.2021.621353621353Multiple Omics Integration Reveals Key Circular RNAs in Hepatocellular CarcinomaZi-Li Huang0Zi-Li Huang1Xiu-Yan Huang2Jin Huang3Xin-Yu Huang4Yong-Hua Xu5Jian Zhou6Zhao-You Tang7Department of General Surgery, Shanghai Jiaotong University Affiliated Sixth People’s Hospital, Shanghai, ChinaDepartment of Radiology, Xuhui District Central Hospital of Zhongshan Hospital, Fudan University, Shanghai, ChinaDepartment of General Surgery, Shanghai Jiaotong University Affiliated Sixth People’s Hospital, Shanghai, ChinaDepartment of Pathology, Shanghai Jiaotong University Affiliated Sixth People’s Hospital, Shanghai, ChinaDepartment of General Surgery, Shanghai Jiaotong University Affiliated Sixth People’s Hospital, Shanghai, ChinaDepartment of Radiology, Xuhui District Central Hospital of Zhongshan Hospital, Fudan University, Shanghai, ChinaLiver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, ChinaLiver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, ChinaBackgroundHCC is one of the most common malignancies with an increasing incidence worldwide, especially in Asian countries. However, even though targeted cancer therapy drugs such as sorafenib and regorafenib are available, the overall outcome of HCC remains unsatisfactory. Thus, it is urgent to investigate the molecular mechanisms of HCC progression, so as to provide accurate diagnostic criteria and therapeutic targets.MethodsRNA-seq data was used to identify and quantify circular RNAs (circRNAs). DESeq2 was used to identify the differentially expressed circRNAs. miRNA binding sites within circRNAs were identified by miRanda. Gene set enrichment analysis (GSEA) was conducted to predict the biological function of circRNAs.ResultsThe differential expression analysis identified 107 upregulated and 95 downregulated circRNAs in HCC tissues. We observed that a differentially expressed circRNA (DE-circRNA), hsa_circ_0141900 was highly negatively correlated with its parental gene RAB1A (PCC < -0.6), which was also closely associated with mTOR signaling pathway. Moreover, we also constructed competing endogenous RNA (ceRNA) network to identify key circRNAs involved in HCC. Notably, hsa_circ_0002130 and hsa_circ_0008774 were highly correlated with the genes involved in gluconeogenesis and HNF3A pathway via the target genes, GOT2 and AR, suggesting that the two circRNAs might regulate these pathways, respectively. Survival analysis revealed that GOT2 was associated with favorable prognosis. Furthermore, high expression of hsa_circ_0002130 was found to inhibit tumor cell growth and promotes GOT2 expression.ConclusionIn summary, the circRNAs highlighted by the integrative analysis greatly improved our understanding of the underlying mechanism of circRNAs in HCC.https://www.frontiersin.org/articles/10.3389/fonc.2021.621353/fullhepatocellular carcinomacircular RNAsmTOR signaling pathwaygluconeogenesisHNF3A pathway |
| spellingShingle | Zi-Li Huang Zi-Li Huang Xiu-Yan Huang Jin Huang Xin-Yu Huang Yong-Hua Xu Jian Zhou Zhao-You Tang Multiple Omics Integration Reveals Key Circular RNAs in Hepatocellular Carcinoma Frontiers in Oncology hepatocellular carcinoma circular RNAs mTOR signaling pathway gluconeogenesis HNF3A pathway |
| title | Multiple Omics Integration Reveals Key Circular RNAs in Hepatocellular Carcinoma |
| title_full | Multiple Omics Integration Reveals Key Circular RNAs in Hepatocellular Carcinoma |
| title_fullStr | Multiple Omics Integration Reveals Key Circular RNAs in Hepatocellular Carcinoma |
| title_full_unstemmed | Multiple Omics Integration Reveals Key Circular RNAs in Hepatocellular Carcinoma |
| title_short | Multiple Omics Integration Reveals Key Circular RNAs in Hepatocellular Carcinoma |
| title_sort | multiple omics integration reveals key circular rnas in hepatocellular carcinoma |
| topic | hepatocellular carcinoma circular RNAs mTOR signaling pathway gluconeogenesis HNF3A pathway |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2021.621353/full |
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