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.