Abstract
Gene fusion, as a prototypical pathognomonic mutation, contributes to genome complexity, and the cis-transcription-induced gene fusions generated by read-through transcription of adjacent genes have been found to be important for tumor development. We screened read-through transcription events from stomach adenocarcinoma RNA-seq data and selected three candidates PHOSPHO2-KLHL23, RPL17-C18orf32, and PRR5-ARHGAP8, to assess their biological role in gastric cancer. The expression of all three read-through fusion transcripts was confirmed in gastric cancer cell lines and paired normal/tumor gastric cancer tissues by real-time quantitative reverse transcription polymerase chain reaction and their expression was found to be significantly higher in the tumor (P < 0.05; n = 75). The correlation between the expression level and clinicopathological information was statistically analyzed. The level of the PHOSPHO2-KLHL23 read-through fusion transcript correlated with the Lauren classification and was significantly associated with the presence of perineural invasion. Overexpression of KLHL23 from PHOSPHO2-KLHL23 read-through transcript led to a significant increase in cell proliferation and resistance to anticancer drug treatment. Silencing of KLHL23 expression decreased cyclin D1 levels. The expression of KLHL23 from prevalent read-through transcripts of PHOSPHO2-KLHL23 in gastric cancer may undermine the efficacy of anticancer drug treatment.