Although Fusion genes have been recognized as an oncogene that affects development and progression of cancer, there are rarely reports of fusion genes in hepatocellular carcinoma (HCC), the third leading cause of cancer mortality worldwide. Advances of RNA sequencing (RNA-Seq) technology offer the ability to screen fusion genes. The current study aimed to determine whether fusion genes are present and affect cancer progression in HCC. Here, the fusion transcripts were identified by using the fusion detection pipeline based on the three different fusion-finder algorithms: SOAPfuse, ChimeraScan, and TopHat-Fusion. Out of 14 potential fusion transcripts that were not previously reported, SLC39A14-PIWIL2 was predicted as a potential oncogenic fusion gene through evaluating the expression of 3’ transcripts. SLC39A14, a metal-ion transporter, is known to maintain metal ion homeostasis by excreting zinc, iron, and manganese in the liver and pancreas, and PIWIL2 has been reported to causes tumorigenesis in organs other than testis. The structure of SLC39A14-PIWIL2 was formed by fusion of SLC39A14 exon 1 and PIWIL2 exons 7–23 on the same chromosome 8 through chromosomal inversion in one HCC patient. The truncated form of PIWIL2 was transcripted by SLC39A14 containing the predictive promoter region from SLC39A14-PIWIL2. Using overexpression system, it was demonstrated that SLC39A14-PIWIL2, wild type PIWIL2 (WT PIWIL2), and truncated PIWIL2 (tPIWIL2) were shown to affect proliferation, colony formation, migration, and invasion in the HCC cell lines (i.e., HepG2 and Huh7).
In conclusion, these results suggest that SLC39A14-PIWIL2 fusion transcript identified by the fusion detection pipeline is a novel SLC39A14-PIWIL2 variant that is expected to play oncogenic roles by expressing truncated form of PIWIL2 in HCC.