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Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
Published on: April 26, 2017
STAU1 exhibits oncogenic characteristics and modulates alternative splicing and gene expression in lung
Ling Zhang1, Zhen Peng1, Wei Ding1
1Department of Respiratory and Critical Care Medicine, People's Hospital of Xinjiang Uygur Autonomous Region, No. 91 Tianchi Road, Tianshan District, Urumqi, 830001, China.
Abstract:
Staufen double-stranded RNA-binding protein 1 (STAU1) plays a significant role in cancer development and is associated with survival outcomes in patients with lung cancer. However, its specific functions and molecular mechanisms in lung adenocarcinoma (LUAD) remain underexplored. We conducted a comprehensive analysis of the role and mechanism of STAU1 in A549 cells via RNA sequencing (RNA-seq) and in vitro experiments. STAU1 is highly expressed in A549 cells, and the proliferation, invasion, and migration capabilities of siSTAU1 cells are markedly inhibited, while the level of apoptosis is increased. Through RNA-seq analysis, we identified 197 differentially expressed genes (DEGs) and 1,362 STAU1-regulated alternative splicing events (ASEs). The DEGs were specifically enriched in cell adhesion pathways, whereas the ASE genes were predominantly associated with cell division and the cell cycle. Furthermore, we validated the expression of several genes related to proliferation, invasion, and migration, as well as the AS patterns. Specifically, the expression levels of CFHR1, KLF2, and RHOB were upregulated in the siSTAU1 samples, whereas the expression of MASTL and STC2 was downregulated. Additionally, the AS patterns of BIN1 and SNHG17 were abnormal, which was corroborated by PCR experiments. Our study suggests that STAU1 has oncogenic characteristics and may modulate these genes to influence the proliferation, invasion, and migration of lung adenocarcinoma cells. This research offers new insights that may contribute to the diagnosis and treatment of LUAD.
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