Dataset Information

Targeting p85β condensates by RNA therapy inhibits liver cancer progression

ABSTRACT: PI3K complex consists of catalytic subunit p110s and regulatory subunit p85s. Emerging evidence indicates that p110-free p85 subunits play pivotal roles in diverse biological processes, including cancer progression. In this study, we demonstrate the oncogenic function and underlying mechanism of p110-free p85β in hepatocellular carcinoma (HCC) development. PIK3R2/p85β is highly expressed in HCC tissues and correlates with worse overall survival of HCC patients. Nuclear p85β, but not its cytoplasmic counterpart, exhibits oncogenic activity. In the nucleus of HCC cells, p85β undergoes liquid-liquid phase separation (LLPS) and specifically accumulates in the fibrillar centers of nucleoli, where it drives HCC progression. Within the nucleolar compartment, p85β directly interacts with and stabilizes POLR1A, the catalytic core subunit of RNA polymerase I, thereby enhancing rRNA biosynthesis and maintaining HCC stemness. Furthermore, we develop an engineered circular RNA that encodes a peptide containing p110α ABD domain, which effectively suppresses HCC tumor growth by simultaneously disrupting p85β/POLR1A condensates and inhibiting PI3K/AKT signaling pathway. Our findings not only elucidate the critical role of p85β biomolecular condensates in HCC tumorigenesis but also establish a novel RNA-based therapeutic strategy for HCC intervention.

ORGANISM(S): Homo sapiens

PROVIDER: GSE291263 | GEO | 2025/05/01

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Although it causes only mild respiratory disease, influenza D virus (IDV) is implicated in bovine respiratory disease complex (BRDC), which is a major cause of economic concern for cattle producers globally. The virus replicates in the upper and lower respiratory tract with virus titre highest in nasal turbinates. We therefore hypothesised that the bovine turbinate (BT) cell line could provide a useful in vitro model to study viral–host interactions. Host gene expression was determined using RNA-Seq. Significantly differentially expressed genes with respect to mock-infected cells were identified using DESeq2 and KEGG pathway analysis used to determine enriched pathways. Psuedotyped viruses were used to show the involvement of intrinsic innate immune responses including IFN-inducible transmembrane (IFITM) proteins in restricting the entry of IAV, ICV and IDV. Localization of bovine IFITM3 was determined using immunofluorescence assay. Pull-down and immunoprecipitation assays were used to detect binding of IDV NS1 to p85β subunit of the PI3K pathway. RNA-Seq demonstrated the involvement of genes related to type I or type III interferon responses in IDV infection of BT cells. Intrinsic innate immune responses including IFN-inducible transmembrane (IFITM) proteins restricted the entry of IAV, ICV and IDV pseudotyped viruses. Determination of the subcellular localization of bovine IFITM3 showed that it has an intracellular cytoplasmic distribution. KEGG pathway analysis of the transcriptomic data showed activation of the PI3K/Akt pathway. This led to the hypothesis that IDV activates the pathway in a similar way to influenza A virus (IAV), by non-structural NS1 protein binding the PI3K p85β subunit. However, pull-down and immunoprecipitation assays did not detect binding of IDV NS1 to p85β; this may be due to amino acid differences in the tyrosine-phosphorylated YXXXM motif that is important in the binding of the IAV NS1 to the p85β subunit. This suggests a different mechanism in preventing apoptosis after IDV infection. In conclusion, this study has shown the efficient replication of IDV in bovine turbinate cells. The study has also shown the involvement of type I interferon responses in immune response to IDV infection of cells of the upper respiratory tract of the cow. There is the involvement of different signalling pathways including the FoXO and PI3K/Akt pathway in IDV infection. Bovine IFITM3 is localised intracellularly and is involved in the restriction of IDV entry.

Dataset Information

Targeting p85β condensates by RNA therapy inhibits liver cancer progression

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets