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Circular ZBTB44-encoded ZBTB44-342aa alleviates osteogenic differentiation of human aortic valve interstitial cells by inhibiting the cGAS-STING pathway

GSE295765 Homo sapiens (human) Non-coding RNA profiling 11 samples Submitted 2025/12/15 Platform GPL24676

At a glance

Non-coding RNA profiling · human · 11 samples

What it is: Non-coding RNA profilingLevels of RNAs that do not code for proteins, such as miRNA or lncRNA.
Organism: Homo sapiens (human)
Samples: 11 samples: 6 × CAVD vs 5 × non-CAVDGroups are read from the sample names, not from the paper. Check the list below.
Data you can get: A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.

Summary (written by the submitters)

Background Circular RNAs (circRNAs) are implicated in various physiopathologic activities and play a crucial role in calcific aortic valve disease (CAVD) progression. However, the role of coding circRNAs in CAVD remains unclear. In this study, we aimed to characterize coding circRNAs and explore their functions in CAVD. Methods We identified circular Zinc finger and BTB domain-containing protein 44 (CircZBTB44) through transcriptome sequencing and characterized its coding capacity through a series of experiments.

Read the full summary ↓

We investigated the biological role of circZBTB44 and its encoded peptide, ZBTB44-342aa, in CAVD, as well as its mechanism of action through in vivo and in vitro experiments. Results We found that circZBTB44 promotes the translation of ZBTB44-342aa through N6-methyladenosine modifications. Functionally, ZBTB44-342aa alleviates mitochondrial DNA (mtDNA) release into the cytoplasm, suppresses the activation of the Cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway, and alleviates the osteogenic differentiation of human aortic valve interstitial cells (HAVICs). In vivo, circZBTB44 adeno-associated virus and STING deprivation alleviated the aortic valve lesions induced in an aortic valve injury (AVI) model. In vitro, the overexpression of circZBTB44 or the exogenous addition of the ZBTB44-342aa recombinant protein inhibited the osteogenic response of HAVICs. Conversely, the siRNA-mediated knockdown of circZBTB44 enhanced this response. Furthermore, H-151-induced inhibition of STING alleviated the osteogenic response of HAVICs, whereas STING activation by dimeric amidobenzimidazole exacerbated this response. ZBTB44-342aa inhibits mitochondrial fission by binding to Insulin-like growth factor 2 mRNA-binding protein 3, which reduces the leakage of mtDNA into the cytoplasm and promotes the stability of calcium/calmodulin-dependent protein kinase 1. This reduction inhibited STING activation and suppressed downstream osteogenic responses. Conclusion This study demonstrates that circZBTB44 encodes a novel peptide, ZBTB44-342, which alleviates CAVD progression by inhibiting the activation of the cGAS-STING signaling pathway. Therefore, circZBTB44 and STING may be potential targets for future therapeutic interventions in CAVD.

This dataset

Open GSE295765 in finder → Find more human RNA-seq datasets →

Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE295765_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓

3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

Also filed as BioProject PRJNA1256331 and SRA study SRP581741. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Study design

6 × CAVD vs 5 × non-CAVD

Supports a between-group comparison across 11 samples.

How we read this: 2 replicated groups read from 11 sample titles; they account for 11 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study

GSM8956989 CAVD-1 CAVD
GSM8956990 CAVD-2 CAVD
GSM8956991 CAVD-3 CAVD
GSM8956992 CAVD-4 CAVD
GSM8956993 CAVD-5 CAVD
GSM8956994 CAVD-6 CAVD
GSM8956995 non-CAVD-1 non-CAVD
GSM8956996 non-CAVD-2 non-CAVD
GSM8956997 non-CAVD-3 non-CAVD
GSM8956998 non-CAVD-4 non-CAVD
GSM8956999 non-CAVD-5 non-CAVD

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