# Expression analysis of circ-AKT3 and circ-EGLN3 in BK polyomavirus-infected kidney transplant recipients: potential biomarkers for viral reactivation

**Authors:** Samar Bizhani, Afsoon Afshari, Ramin Yaghobi, Jamshid Roozbeh

PMC · DOI: 10.1186/s12879-025-11911-5 · BMC Infectious Diseases · 2025-11-05

## TL;DR

This study investigates how two circular RNAs, circ-AKT3 and circ-EGLN3, may act as potential biomarkers for BK polyomavirus reactivation in kidney transplant recipients.

## Contribution

The study identifies circ-AKT3 and circ-EGLN3 as novel potential biomarkers for detecting BKPyV reactivation in kidney transplant patients.

## Key findings

- circ-AKT3 and circ-EGLN3 levels were significantly lower in BKPyV-infected kidney transplant recipients.
- Target miRNAs (miR-1299 and miR-296-3p) were elevated in infected individuals compared to non-infected ones.
- ROC analysis showed that these circRNAs can effectively differentiate BKPyV-infected from non-infected individuals.

## Abstract

BK polyomavirus (BKPyV) establishes latent human infections, with reactivation linked to the cellular immune response, particularly in kidney transplant recipients (KTRs). Circular RNAs (circRNAs) and microRNAs (miRNAs), classes of noncoding RNAs, are involved in the pathogenesis of kidney diseases and viral infections. CircRNAs act as miRNA “sponges,” diminishing miRNA functions. This study explores the relationship between BKPyV infection and circ-EGLN3 and circ-AKT3, their miRNA targets (miR-1299, miR-296-3p), and their linear counterparts (EGLN3, AKT3), along with miRNA targets (IRF7, CDH1).

This cross-sectional study included 20 KTRs, divided into 10 BKPyV-infected and 10 non-infected individuals, with an additional control group of 20 healthy individuals. Expression levels of circRNAs, parental genes, and target miRNAs were assessed in blood and urine samples using SYBR Green real-time PCR.

In KTRs with active BKPyV infection, circ-AKT3 and circ-EGLN3 levels were significantly reduced, while their target miRNAs were elevated in both blood and urine compared to non-infected KTRs. ROC curve analysis demonstrated that these circRNAs could significantly differentiate BKPyV-infected individuals from non-infected groups.

This research has established the significance of circular RNAs, particularly circ-AKT3 and circ-EGLN3, and suggests that with additional investigation, these molecules may serve as biomarkers for active BKPyV infection in KTRs, thereby improving the comprehension of BKPyV reactivation.

Not applicable.

## Linked entities

- **Genes:** EGLN3 (egl-9 family hypoxia inducible factor 3) [NCBI Gene 112399], AKT3 (AKT serine/threonine kinase 3) [NCBI Gene 10000], IRF7 (interferon regulatory factor 7) [NCBI Gene 3665], CDH1 (cadherin 1) [NCBI Gene 999]
- **Diseases:** kidney disease (MONDO:0001343)

## Full-text entities

- **Genes:** MIR1299 (microRNA 1299) [NCBI Gene 100302167] {aka MIRN1299, hsa-mir-1299}, CDH1 (cadherin 1) [NCBI Gene 999] {aka Arc-1, BCDS1, CD324, CDHE, ECAD, LCAM}, AKT3 (AKT serine/threonine kinase 3) [NCBI Gene 10000] {aka MPPH, MPPH2, PKB-GAMMA, PKBG, PRKBG, RAC-PK-gamma}, IRF7 (interferon regulatory factor 7) [NCBI Gene 3665] {aka IMD39, IRF-7, IRF-7H, IRF7A, IRF7B, IRF7C}, EGLN3 (egl-9 family hypoxia inducible factor 3) [NCBI Gene 112399] {aka HIFP4H3, HIFPH3, PHD3}
- **Diseases:** infected (MESH:D007239), BK polyomavirus (MESH:D027601), viral infections (MESH:D014777), kidney diseases (MESH:D007674)
- **Species:** Betapolyomavirus hominis (species) [taxon 1891762], Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12590913/full.md

## References

24 references — full list in the complete paper: https://tomesphere.com/paper/PMC12590913/full.md

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Source: https://tomesphere.com/paper/PMC12590913