Z Gastroenterol 2020; 58(01): e53
DOI: 10.1055/s-0039-3402246
Poster Visit Session IV Tumors: Saturday, February 15, 2020, 8:30 am – 09:15 am, Lecture Hall P1
Georg Thieme Verlag KG Stuttgart · New York

LINC00152 drives a ceRNA network in human hepatocellular carcinoma

R Pellegrino
1   Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany
,
F Ticconi
2   Computational Biolology, IZKF Aachen and Helmholtz Institute for Biomedical Engineering, Aachen, Germany
,
B Skawran
3   Institute of Human Genetics, Hannover Medical School, Hannover, Germany
,
M Castoldi
4   Division of Gastroenterology, Hepatology and GI Oncology, University Hospital RWTH, Aachen, Germany
,
P Schirmacher
1   Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany
,
I Costa
2   Computational Biolology, IZKF Aachen and Helmholtz Institute for Biomedical Engineering, Aachen, Germany
,
T Longerich
1   Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
03 January 2020 (online)

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Increasing evidences have assigned essential roles in cellular processes to the long non-coding RNAs (lncRNAs). These include chromatin organization, gene transcription, RNA turnover and maturation. More interestingly, lncRNAs may act as miRNA sponges thereby affecting miRNA bioavailability, which in turn alters target gene expression. By integrating methylome and gene expression data of human hepatocellular carcinoma (HCC) samples we observed methylation-dependent downregulation of LINC00152 in human HCCs compared to normal liver. Here, we investigated whether LINC00152 forms a competing endogenous RNA (ceRNA) network in human HCC.

Using in silico analyses (http://www.mircode.org) 24 miRNA candidates were predicted to bind to LINC00152. Of these, expression of 22 miRNAs was detected in a cohort of human HCC samples. Next, the genes potentially regulated by these miRNA candidates were determined using StarBase. Based on the criterion to be predicted by at the least two different algorithms (http://targetscan.org, http://pictar.mdcberlin.de, http://www.microrna.org, https://cm.jefferson.edu/rna22v2/) 2.664 genes were identified as potential target genes potentially regulated by a LINC00152-driven ceRNA network. Based on the statistical association between putative miRNAs and target genes in our human HCC, miR.23a.3 p, miR.125a.5 p, miR.125b.5 p, miR.223.3 p, and miR.143.3 p were selected as top miRNA and STK39, FAM60A, FUT4, PALLD, and MAP3K1 as top gene candidates. In line, decreased expression of these target genes was detected in LINC00152-deficient HuH7 cells compared to controls. More interestingly, RNA immunoprecipitation revealed that LINC00152 co-occurs with all top 10 candidate miRNAs in ribonucleoprotein complexes (miRNPs). Inhibition or overexpression of LINC00152 in human HCC cell lines decreased or increased respectively cell growth compared to the corresponding control cells. Furthermore, high LINC00152 expression level was associated with shorter survival of HCC patients after liver resection.

All together our data demonstrate that LINC00152 drives human hepatocarcinogenesis via a ceRNA network.