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Competing endogenous RNA screening based on lncRNA-mRNA co-expression profile in HBV-associated hepatocarcinogenesis

Author: Wen Quan, Yang Yao, Chen Xianhua, Pan Xiaodong, Han Qi, Wang Dong, Li Xiaohui, Deng Youcai, Zhou Jihong

OBJECTIVE: To profile the liver cancer specific lncRNAs and ceRNA networks of HBV-associated HCG and also test the role of compound K on the expression of identified ceRNA networks. METHODS: Based on the lncRNA and mRNA microarray data of HBV-associated liver cancer, the current study profiles the cancer specific lncRNAs and ceRNA networks of HBV-associated HCG through comprehensive application of RegRNA 2, miRTarBase and Pearson correlation coefficient analysis. Compound K treated liver cancer cells were harvest for analyzing the transcriptional levels of both EHHADH-AS1 and ENTPD5. RESULTS: The results revealed 11 Encyclopedia of DNA Elements (ENCODE) annotated lncRNAs that were differentially expressed in the process of HBV-associated HCG. Among these lncRNAs, we constructed 95 potential ceRNA networks that with highly positive correlated expression profile between the interacted lncRNAs and mRNAs (Pearson correlation coefficient ≥ 0.7). Of note, two HBV-associated ceRNA networks, EHHADH-AS1-hsa-miR-4459-ENTPD5 and LINC01018-hsa-miRNA-574-5p-G6PC with Pearson correlation coefficient ≥ 0.9, may play a critical role in hepatocellular carcinoma development, further supported by experimental evidence. Interestingly, compound K, an intestinal bacterial metabolite of ginseng protopanaxadiol saponin of which have been proven to promote apoptosis of human hepatocellular carcinoma, impeded the down-regulation of EHHADH-AS1 in liver cancer cell lines, HepG3B, Huh-7 and plc/prf/5 cells. CONCLUSION: Comprehensive application of co-expression network analysis and RNA interaction prediction will be a good strategy to find new potential ceRNA networks involved in the process of human diseases.

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