Dataset Information

ADAR1 expression is associated with cervical cancer progression and negatively regulates NK cell activity

ABSTRACT: ADAR1 edits double-stranded (ds) RNAs by deaminating adenosines into inosines preventing aberrant activation of innate immunity by endogenous dsRNAs, which may resemble viral structures. Several tumors exploit ADAR1 to evade immune surveillance; indeed, its deletion reduces tumor viability and reshapes infiltrating leukocytes. Here, we investigated the role of ADAR1 in immune evasion mechanisms during cervical cancer (CC) progression. Patients’ biopsies showed higher ADAR1 expression already in pre-malignant (SIL) lesions, and a substantially reduced percentage of infiltrating CD7+ innate cells in in situ and invasive carcinomas, compared to normal mucosa, with CD56+ NK cells showing phenotypic alterations that might impact their functional responses. In CC-derived cell lines (SiHa, CaSki), ADAR1 silencing reduced cell proliferation, an effect further enhanced by exogenous IFNbeta administration. It also induced pro-inflammatory gene expression, as demonstrated by RNAseq analysis, and conditioned supernatants collected from these cells activated several NK cell effector functions. NK cell infiltration and activation was also confirmed in organotypic 3D tissue models of SiHa cells knocked-out for ADAR1. In conclusion, ADAR1 expression increases with CC progression and is accompanied by alterations of tumor-infiltrating NK cells, but its silencing in CC-derived cell lines potentiated anti-tumor NK cell activities. Thus, ADAR1 inhibition may represent a therapeutic perspective for CC and possibly other malignancies.

ORGANISM(S): Homo sapiens

PROVIDER: GSE297095 | GEO | 2025/05/21

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Cervical cancer (CC) is one of the most common malignancy in women worldwide. It is characterized by a natural continuous phenomenon, that is, it is in the initial stage of HPV infection, progresses to intraepithelial neoplasia, and then develops into invasion and metastasis. Determining the complexity of tumor microenvironment (TME) can deepen our understanding of lesion progression and provide novel therapeutic strategies for CC. We performed the single-cell RNA sequencing on the normal cervix, intraepithelial neoplasia, primary tumor and metastatic lymph node tissues to describe the composition, lineage, and functional status of immune cells and mesenchymal cells at different stages of CC progression. A total of 59913 single cells were obtained and divided into 9 cellular clusters, including immune cells (T/NK cells, macrophages, B cells, plasma cells, mast cells and neutrophils) and mesenchymal cells (endothelial cells, smooth muscle cells and fibroblasts). Our results showed that there were distinct cell subpopulations in different stages of CC. High-stage intraepithelial neoplasia (HSIL) tissue exhibited a low, recently activated TME, and it was characterized by high infiltration of tissue-resident CD8 T cell, effector NK cells, Treg, DC1, pDC, and M1-like macrophages. Tumor tissue displayed high enrichment of exhausted CD8 T cells, resident NK cells and M2-like macrophages, suggesting immunosuppressive TME. Metastatic lymph node consisted of naive T cell, central memory T cell, circling NK cells, cytotoxic CD8+ T cells and effector memory CD8 T cells, suggesting an early activated phase of immune response. This study is the first to delineate the transcriptome profile of immune cells during CC progression using single-cell RNA sequencing. Our results indicated that HSIL exhibited a low, recently activated TME, tumor displayed immunosuppressive statue, and metastatic lymph node showed early activated phase of immune response. Our study enhanced the understanding of dynamic change of TME during CC progression and has implications for the development of novel treatments to inhibit the initiation and progression of CC.

Dataset Information

ADAR1 expression is associated with cervical cancer progression and negatively regulates NK cell activity

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets