DDX17 modulates the expression and alternative splicing of genes involved in apoptosis and proliferation in lung adenocarcinoma cells

Background. The DEAD-box RNA-binding protein (RBP) DDX17 has been found to be involved in the tumorigenesis of many types of cancers. However, the role of DDX17 in lung adenocarcinoma (LUAD) remains unclear.Methods. We silenced DDX17 expression in A549 LUAD cells by small interfering RNA (siRNA). Cell proliferation and apoptosis assays were performed to explore the functions of DDX17. Knockdown of DDX17 by siRNA significantly inhibited proliferation and induced apoptosis in A549 cells. We used high-throughput RNA sequencing (RNA-seq) to identify differentially expressed genes (DEGs) and alternative splicing (AS) events in DDX17 knockdown LUAD cells. Results. DDX17 knockdown increased the expression levels of proapoptotic genes and decreased those of proproliferative genes. Moreover, the DDX17-regulated AS events in A549 cells revealed by computational analysis using ABLas software were strongly validated by quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and were also validated by analysis of The Cancer Genome Atlas (TCGA)-LUAD dataset. These findings suggest that DDX17 may function as an oncogene by regulating both the expression and AS of proliferation-and apoptosis-associated genes in LUAD cells. Our findings may offer new insights into understanding the molecular mechanisms of LUAD and provide a new therapeutic direction for LUAD.

Automated summary

The study found that DDX17 plays a role in promoting cell proliferation and inhibiting apoptosis in lung adenocarcinoma (LUAD). RNA sequencing identified differential gene expression and alternative splicing events in DDX17 knockdown LUAD cells. The findings suggest that DDX17 regulates the expression and alternative splicing of proliferation- and apoptosis-associated genes in LUAD cells, providing new insights into the molecular mechanisms of LUAD and potential therapeutic directions.