Abstract
Long non-coding RNAs (lncRNAs) regulate oncogenesis by inducing methylation of CpG islands to silence target genes. Here we show that the lncRNA PCAT-14 is overexpressed in patients with hepatocellular carcinoma (HCC), and is associated with a poor prognosis after surgery. Our results demonstrate that PCAT-14 promotes proliferation, invasion, and cell cycle arrest in HCC cells. In addition, PCAT-14 inhibits miR-372 expression by inducing methylation of the miR-372 promoter. Simultaneously, miR-372 eliminates the effects of PCAT-14 on proliferation, invasion, and cell cycle in HCC cells. Moreover, PCAT-14 regulates expression of ATAD2 and activation of the Hedgehog pathway via miR-372. These findings indicate that PCAT-14 plays an important role in HCC, and may serve as a novel prognostic factor and therapeutic target.
Highlights
Hepatocellular carcinoma (HCC) is one of the most prevalent tumor types with the highest mortality rate [1]
Our results demonstrate that the prostate cancer-associated transcripts (PCATs)-14 expression is associated with hepatocellular carcinoma (HCC) metastasis, tumor size, and TNM stage, suggesting that PCAT-14 may be involved in the tumorigenesis and progression of HCC
Trans-well assay indicated that miR-372 could block the influence of PCAT14 on cellular invasion and migration (Figure 2C, 2D). These results suggest that PCAT-14 regulates HCC cell proliferation, cycle, and invasion depending on miR-372
Summary
Hepatocellular carcinoma (HCC) is one of the most prevalent tumor types with the highest mortality rate [1]. Many HCC patients do not have any symptoms until an advanced stage [3]. Even though HCC prognosis has improved thanks to the development of effective surgical techniques and diagnostic methods over recent years, long-term prognosis is still unsatisfactory largely due to the high recurrence (50–70% at 5 years) [4, 5]. There is an urgent need to identify valuable diagnostic and prognostic biomarkers to improve clinical outcomes and develop effective individual therapeutic strategies for patients with HCC. LncRNAs, such as HULC, HOTAIR, and DBH-AS1 represent an emerging group, which may regulate HCC cell proliferation, migration, and apoptosis [11,12,13]
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