Newly identified piRNA linked to congenital heart disease in foetal rats

A small RNA molecule has emerged as a possible lead in the search for better ways to detect congenital heart disease (CHD) before birth. In a study published in Cell Biology and Toxicology, researchers identified a PIWI-interacting RNA, hsa_piR_004152, which they named CHD-associated piRNA (CHDPIR), and found it significantly upregulated in maternal plasma-derived extracellular vesicles (EVs) from pregnancies affected by foetal CHD and in heart tissue from foetuses with CHD.

piRNAs are regulatory molecules whose roles in CHD had remained largely unknown. To probe CHDPIR’s function, the team overexpressed it in AC16 cardiomyocytes. This disrupted iron homeostasis and promoted ferroptosis-associated oxidative changes, effects that were partially reversed by ferrostatin-1, a ferroptosis inhibitor. The results point to a specific cell-level mechanism linking the RNA to oxidative injury in heart muscle cells.

Mechanistic experiments suggested how CHDPIR acts. In vitro binding assays showed that CHDPIR bound directly to the RNA-binding protein splicing factor proline- and glutamine-rich (SFPQ). CHDPIR overexpression reduced SFPQ occupancy at the promoter of colony-stimulating factor 2 receptor subunit beta (CSF2RB) and attenuated SFPQ-mediated transcriptional activation of that gene, implicating the SFPQ–CSF2RB axis in the regulation of cardiomyocyte iron homeostasis.

The researchers also tested CHDPIR in an experimental model. In foetal rats with nitrofen-induced CHD, knocking down CHDPIR attenuated disturbances in iron homeostasis and ferroptosis-associated protein changes and improved cardiac function. These in vivo findings, obtained in a chemically induced animal model, support the molecule’s potential as a target for intervention, though the authors frame the work as a basis for further investigation of CHDPIR-directed approaches rather than an established therapy.

Overall, the study supports CHDPIR as a potential maternal plasma EV biomarker for prenatal CHD assessment and offers insight into molecular alterations associated with the condition. As with any early-stage biomarker and mechanistic research, the findings come from cell culture, in vitro binding experiments and a rat model, and will require further validation before any clinical use in prenatal screening or treatment.

Subject of Research: A piRNA biomarker and its SFPQ–CSF2RB mechanism in congenital heart disease

Article Title: CHDPIR: a piRNA with biomarker and therapeutic potential in congenital heart disease

Article References: Sun, X., Wang, G., Gu, H., Zhang, N., Yang, W., Luo, W., Wang, Y., & Yuan, Z. (2026). CHDPIR: a piRNA with biomarker and therapeutic potential in congenital heart disease. Cell Biology and Toxicology. https://doi.org/10.1007/s10565-026-10293-x

Image Credits: AI Generated

DOI: 10.1007/s10565-026-10293-x

Keywords: piRNA, CHDPIR, congenital heart disease, extracellular vesicles, ferroptosis, SFPQ, CSF2RB, iron homeostasis, biomarker, cardiomyocytes, prenatal diagnosis, nitrofen-induced CHD