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Archive > Volume 28 Issue 9 > 2021,28(9):914-919. DOI:10.3872/j.issn.1007-385X.2021.09.008 Prev Next
Clinical Research
Screening of prognosis-related enhancer RNAs and their corresponding target genes in patients with hepatocellular carcinoma and its prognostic significance
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Abstract:
Objective: To screen the enhancer RNAs (eRNAs) and their corresponding target genes related to the prognosis hepatocellular carcinoma (HCC), and to explore their regulatory effect and function. Methods: The transcript data and clinical data of HCC were downloaded from UCSC database to extract the expression matrix of eRNAs and their predicted corresponding target genes. Kaplan-Meier and Spearman correlation analysis were used to screen HCC prognosis-related eRNAs and the target genes, and the least absolute shrinkage and selection operator (LASSO) regression analysis and multivariate Cox multiple regression analysis were utilized to construct a HCC prognostic risk scoring system. A short interfering RNA (siRNA) targeting eRNA AP003469.2 was designed and synthesized to transfect liver cancer SMMC-7721 cells. Then, RT-PCR was used to verify the knockdown efficiency, qPCR was used to detect the expression of the target gene YWHAZ, and CCK-8 was adopted to examine the proliferation of SMMC-7721 cells after transfection. Results: Four prognosis-related genes were screened, including two eRNAs (AP003469.2 and SPRY4-AS1) and two target genes (PPARGC1A and SLC2A1) (P<0.05). Among them, the high expression of PPARGC1A indicated a better prognosis, while the high expression of AP003469.2, SPRY4-AS1 and SLC2A1 genes indicated a poor prognosis. The prognostic risk scoring system constructed based on the 4 genes exhibited AUC of 0.730, 0.699 and 0.679 at the 1st, 3rd and the 5th year respectively, indicating good predictive performance of the system. After AP003469.2 knockdown in SMMC-7721 cells, the expression of its predicted target gene YWHAZ did not change significantly, and it had no significant effect on the proliferation of SMMC-7721 cells. Conclusion: Among the 4 key genes were screened out based on bioinformatics analysis, eRNA AP003469.2 is a biomarker with high prognostic performance for HCC; however, it has no cancer-promoting function or regulatory effect on YWHAZ.
Keywords:
hepatocellular carcinoma (HCC) ; SMMC-772 cell ; bioinformatics ; prognosis ; enhancer RNA ; target gene
Project Supported:
Project supported by the Natural Science Foundation of Tianjin City (No. 20JCYBJC01310), and the Tianjin Major Science and Technology Project for Prevention and Treatment of Major Disease (No. 19ZXDBSY00010)
