HNRNPU promotes the progression of triple-negative breast cancer via RNA transcription and alternative splicing mechanisms.
Bo-Yue HanZhebin LiuXin HuHong LingPublished in: Cell death & disease (2022)
Triple-negative breast cancer (TNBC) is a great detriment to women's health due to the lack of effective therapeutic targets. In this study, we employed an integrated genetic screen to identify a pivotal oncogenic factor, heterogeneous nuclear ribonucleoprotein U (HNRNPU), which is required for the progression of TNBC. We elucidated the pro-oncogenic role of HNRNPU, which can induce the proliferation and migration of TNBC cells via its association with DEAD box helicase 5 (DDX5) protein. Elevated levels of the HNRNPU-DDX5 complex prohibited the intron retention of minichromosome maintenance protein 10 (MCM10) pre-mRNA, decreased nonsense-mediated mRNA decay, and activated Wnt/β-catenin signalling; on the other hand, HNRNPU-DDX5 is located in the transcriptional start sites (TSS) of LIM domain only protein 4 (LMO4) and its upregulation promoted the transcription of LMO4, consequently activating PI3K-Akt-mTOR signalling. Our data highlight the synergetic effects of HNRNPU in RNA transcription and splicing in regulating cancer progression and suggest that HNRNPU may act as a potential molecular target in the treatment of TNBC.
Keyphrases
- transcription factor
- binding protein
- cell proliferation
- protein protein
- induced apoptosis
- healthcare
- signaling pathway
- stem cells
- amino acid
- epithelial mesenchymal transition
- high throughput
- human health
- squamous cell carcinoma
- risk assessment
- gene expression
- small molecule
- copy number
- dna methylation
- endoplasmic reticulum stress
- squamous cell
- long non coding rna
- climate change
- lymph node metastasis
- replacement therapy
- insulin resistance
- heat stress