There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.
Abstract
LncRNA ANCR plays important roles in the modulation of epithelial mesenchymal transition
(EMT) and tumour metastasis in many tumours. However, the role of ANCR in regulating
hepatocellular carcinoma (HCC) metastasis is still not known. The current study aims
to investigate the underlying mechanism for tumour oncogenesis of ANCR in HCC metastasis.
HCC cell proliferation and migration/invasion were measured by MTT and Transwell assays.
Xenograft model was established to determine the effect of ANCR on HCC growth and
metastasis. ChIP assay was used to detect the H3 and H4 histone acetylation levels
at the ANCR promoter region. RNA pull-down and RIP assay was performed to analyse
the relationship between ANCR and heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1).
Dual-luciferase reporter gene assay was conducted to determine the interaction between
ANCR and miR-140-3p. The results indicated that ANCR was highly expressed in HCC tissues
and cells, which promoted the proliferation and migration/invasion of HCC cells.
In vivo experiments showed interfering ANCR suppressed the growth and metastasis
of HCC. H3/H4 histone acetylation levels at the ANCR promoter region were elevated
in HCC tissues and cells, and interfering histone deacetylases 3 (HDAC3) significantly
up-regulated ANCR expression. ANCR could bind to HNRNPA1, and promoted the expression
of HNRNPA1 through regulating its degradation. In addition, ANCR upregulated the expression
of HNRNPA1 through sponging miR-140-3p. Finally, we found that ANCR promoted the EMT
and invasion/migration of HCC cells through regulating HNRNPA1. In conclusion, ANCR
promoted HCC metastasis by upregulating HNRNPA1, inhibiting HNRNPA1 degradation and
sponging miR-140-3p.