Overexpression of KLHL23 protein from read-through transcription ofPHOSPHO2-KLHL23in gastric cancer increases cell proliferation.
Gene fusion, as a prototypical pathognomonic mutation, contributes to genome complexity, and thecis-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 candidatesPHOSPHO2-KLHL23, RPL17-C18orf32, andPRR5-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 thePHOSPHO2-KLHL23read-through fusion transcript correlated with the Lauren classification and was significantly associated with the presence of perineural invasion. Overexpression of KLHL23 fromPHOSPHO2-KLHL23read-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 ofPHOSPHO2-KLHL23in gastric cancer may undermine the efficacy of anticancer drug treatment.
Precision Medicine Branch Research Institute National Cancer Center Goyang Gyeonggi-do Korea; Department of Environmental Medical Biology Institute of Tropical Medicine Yonsei University College of Medicine Seoul Korea.
Eun-Seok
ES
Choi
Precision Medicine Branch Research Institute National Cancer Center Goyang Gyeonggi-do Korea.
Hanna
H
Lee
Cancer Cell and Molecular Biology Branch Research Institute National Cancer Center Goyang Gyeonggi-do Korea.
Chang-Hun
0000-0002-4083-2077
CH
Lee
Precision Medicine Branch Research Institute National Cancer Center Goyang Gyeonggi-do Korea.
Sung-Ho
SH
Goh
PHOPHO2‐KLHL23; gastric cancer; read‐through transcription