Received:09 May 2018,
Published:15 November 2018
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Fan LIANG, Quan WEN, Zongwei TANG, et al. Roles and mechanisms of long non-coding RNA EHHADH-AS1 in HBV+ hepatocellular carcinoma[J]. Journal of Third Military Medical University, 2018, 40(21): 1922-1931.
Fan LIANG, Quan WEN, Zongwei TANG, et al. Roles and mechanisms of long non-coding RNA EHHADH-AS1 in HBV+ hepatocellular carcinoma[J]. Journal of Third Military Medical University, 2018, 40(21): 1922-1931. DOI: 10.16016/j.1000-5404.201805071.
Objective
2
To analyze the roles and mechanisms of long non-coding RNA (lncRNA) EHHADH-AS1 in the development of hepatitis B virus positive (HBV
+
) hepatocellular carcinoma (HCC).
Methods
2
In the data of lncRNA and mRNA microarray data in GEO (GSE54238)
the expression level of EHHADH-AS1 in liver tissues of health donors
early stage hepatocellular carcinoma and advanced hepatocellular carcinoma patients were compared. Secondly
coding genes co-expressed with EHHADH-AS1 were identified by Pearson correlation coefficient analysis with |correlation|≥0.7. Gene Ontology (GO) and The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the coding genes co-expressed with EHHADH-AS1 were also performed. Thirdly
Gene Set Enrichment Analysis (GSEA) was further used to analyze the enriched KEGG pathways in HCC patients with higher or lower expression of EHHADH-AS1. Lastly
siRNA technique was applied to knock down EHHADH-AS1 expression in HCC cell line HepG2 and Huh7 to explore the role of EHHADH-AS1 on cell viability
proliferation and cell cycle.
Results
2
The expression of EHHADH-AS1 was significantly decreased in samples of HBV
+
HCC patients
especially in the advanced ones. There is 343 coding genes co-expressed with EHHADH-AS1. The genes negatively associated with EHHADH-AS1 were mainly involved in the cell cycle
cell cycle processes
mitotic cell cycle and DNA replication-related pathways. Similar findings were also found in GSEA's comparative analysis of HBV-associated HCC tissues in both the EHHADH-AS1 high and low expression groups. Experimental studies revealed that knockdown of EHHADH-AS1 expression in HepG2 and Huh7 cells significantly increased cell viability
proliferation
and proportion of cells in S phase.
Conclusion
2
EHHADH-AS1 inhibits the cell cycle of HCC cells
which suppresses the proliferation and viability of tumor cells. This suggests that EHHADH-AS1 plays a key role in the occurrence and development of HBV-related HCC and is expected to become a new diagnostic and prognostic indicator for HBV-related HCC.
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