Role of UPF1 in lncRNA-HEIH regulation for hepatocellular carcinoma therapy.
Hyunho ChaMinwoo KimNarae AhnSeong Dong JeongElizaveta IgnatovaSung Wook ChiHyeon Ho KimJungwook HwangPublished in: Experimental & molecular medicine (2024)
UPF1, a novel posttranscriptional regulator, regulates the abundance of transcripts, including long noncoding RNAs (lncRNAs), and thus plays an important role in cell homeostasis. In this study, we revealed that UPF1 regulates the abundance of hepatocellular carcinoma upregulated EZH2-associated lncRNA (lncRNA-HEIH) by binding the CG-rich motif, thereby regulating hepatocellular carcinoma (HCC) tumorigenesis. UPF1-bound lncRNA-HEIH was susceptible to degradation mediated by UPF1 phosphorylation via SMG1 and SMG5. According to analysis of RNA-seq and public data on patients with liver cancer, the expression of lncRNA-HEIH increased the levels of miR-194-5p targets and was inversely correlated with miR-194-5p expression in HCC patients. Furthermore, UPF1 depletion upregulated lncRNA-HEIH, which acts as a decoy of miR-194-5p that targets GNA13, thereby promoting GNA13 expression and HCC proliferation. The UPF1/lncRNA-HEIH/miR-194-5p/GNA13 regulatory axis is suggested to play a crucial role in cell progression and may be a suitable target for HCC therapy.
Keyphrases
- long non coding rna
- poor prognosis
- single cell
- rna seq
- long noncoding rna
- end stage renal disease
- healthcare
- binding protein
- cell therapy
- ejection fraction
- chronic kidney disease
- newly diagnosed
- signaling pathway
- mental health
- emergency department
- peritoneal dialysis
- prognostic factors
- electronic health record
- big data
- machine learning
- bone marrow
- dna binding