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Analysis of competing endogenous RNA network identifies a poorly differentiated cancer‐specific RNA signature for hepatocellular carcinoma
Author(s) -
Chen QiFeng,
Huang Tao,
SiTu QiJiao,
Wu Peihong,
Shen Lujun,
Li Wang,
Huang Zilin
Publication year - 2020
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.29454
Subject(s) - competing endogenous rna , microrna , long non coding rna , biology , gene silencing , nomogram , hepatocellular carcinoma , rna , messenger rna , hccs , cancer research , computational biology , oncology , gene , genetics , medicine
Plenty of evidence has suggested that long noncoding RNAs (lncRNAs) play a vital role in competing endogenous RNA (ceRNA) networks. Poorly differentiated hepatocellular carcinoma (PDHCC) is a malignant phenotype. This paper aimed to explore the effect and the underlying regulatory mechanism of lncRNAs on PDHCC as a kind of ceRNA. Additionally, prognosis prediction was assessed. A total of 943 messenger RNAs (mRNAs), 86 miRNAs, and 468 lncRNAs that were differentially expressed between 137 PDHCCs and 235 well‐differentiated HCCs were identified. Thereafter, a ceRNA network related to the dysregulated lncRNAs was established according to bioinformatic analysis and included 29 lncRNAs, 9 miRNAs, and 96 mRNAs. RNA‐related overall survival (OS) curves were determined using the Kaplan‐Meier method. The lncRNA ARHGEF7‐AS2 was markedly correlated with OS in HCC ( P = .041). Moreover, Cox regression analysis revealed that patients with low ARHGEF7‐AS2 expression were associated with notably shorter survival time ( P = .038). In addition, the area under the curve values of the lncRNA signature for 1‐, 3‐, and 5‐year survival were 0.806, 0.741, and 0.701, respectively. Furthermore, a lncRNA nomogram was established, and the C‐index of the internal validation was 0.717. In vitro experiments were performed to demonstrate that silencing ARHGEF7‐AS2 expression significantly promoted HCC cell proliferation and migration. Taken together, our findings shed more light on the ceRNA network related to lncRNAs in PDHCC, and ARHGEF7‐AS2 may be used as an independent biomarker to predict the prognosis of HCC.