# Microarray profile of circular RNAs identifies CBT15_circR_28491 and T helper cells as new regulators for deep vein thrombosis

**Authors:** Weiwei Chen, Ying Zhu, Sihua Niu, Yan Zhou, Jian Chang, Shujie Gan

PMC · DOI: 10.3389/fcvm.2025.1578711 · 2025-06-30

## TL;DR

This study identifies a specific circular RNA and T helper cells as potential regulators in deep vein thrombosis, offering new insights for managing the condition.

## Contribution

The study introduces CBT15_circR_28491 and T helper cells as novel regulators in deep vein thrombosis.

## Key findings

- 421 circRNAs and 1,082 mRNAs were differentially expressed in DVT.
- CBT15_circR_28491-rno-miR-139-3p-Kif18a/Cdca8/Nek2 is identified as a potential target for DVT management.

## Abstract

Deep vein thrombosis (DVT) is the third most common cardiovascular disorder and can lead to high mortality and morbidity. This study aimed to clarify the molecular and immune characteristics of circular RNAs (circRNAs) and messenger RNAs (mRNAs) in DVT progression.

DVT-associated dataset GSE148333 was downloaded to screen differentially expressed circRNAs and mRNAs using the limma package. DVT-related modules/genes were then filtered using WGCNA. Subsequently, key hub genes associated with DVT were determined using four algorithms: MCC, MNC, EPC, and DEGREE. A circRNA–miRNA–hub gene network was then constructed, and the relationship between the DVT-related hub genes and immunity was analyzed. Finally, a DVT rat model was established to verify the expression of critical circRNAs and hub genes using real-time quantitative PCR.

A total of 421 circRNAs and 1,082 mRNAs were differentially expressed in DVT. Among these, 235 circRNAs and 207 mRNAs were identified as DVT-related and were significantly enriched in signaling pathways including NOD-like receptor, mTOR, FoxO, p53, and cell cycle. Thereafter, 17 important hub genes were obtained, including Birc5, Plk4, Dlgap5, Spag5, Cdca2, Ccnb1, Cdca8, Kif18a, Kif2c, Espl1, Cenpu, Cdc20, Ncapg, Asf1b, Nek2, Aurkb, and Cenpw. Subsequently, 227 circRNA–miRNA pairs and 84 miRNA–hub gene pairs were included to construct a circRNA–miRNA–hub gene network, containing CBT15_circR_28491-rno-miR-139-3p-Kif18a/Cdca8/Nek2. Eight immune cell types showed differential infiltration levels in DVT and controls, with T helper cells positively related with all 17 hub genes.

This study offers valuable information about circRNAs and mRNAs in DVT, identifying CBT15_circR_28491-rno-miR-139-3p-Kif18a/Cdca8/Nek2 as a potential target for DVT management.

## Linked entities

- **Genes:** BIRC5 (baculoviral IAP repeat containing 5) [NCBI Gene 332], PLK4 (polo like kinase 4) [NCBI Gene 10733], DLGAP5 (DLG associated protein 5) [NCBI Gene 9787], SPAG5 (sperm associated antigen 5) [NCBI Gene 10615], CDCA2 (cell division cycle associated 2) [NCBI Gene 157313], CCNB1 (cyclin B1) [NCBI Gene 891], CDCA8 (cell division cycle associated 8) [NCBI Gene 55143], KIF18A (kinesin family member 18A) [NCBI Gene 81930], KIF2C (kinesin family member 2C) [NCBI Gene 11004], ESPL1 (extra spindle pole bodies like 1, separase) [NCBI Gene 9700], CENPU (centromere protein U) [NCBI Gene 79682], CDC20 (cell division cycle 20) [NCBI Gene 991], NCAPG (non-SMC condensin I complex subunit G) [NCBI Gene 64151], ASF1B (anti-silencing function 1B histone chaperone) [NCBI Gene 55723], NEK2 (NIMA related kinase 2) [NCBI Gene 4751], AURKB (aurora kinase B) [NCBI Gene 9212], CENPW (centromere protein W) [NCBI Gene 387103]

## Full-text entities

- **Genes:** Ccnb1 (cyclin B1) [NCBI Gene 25203], Espl1 (extra spindle pole bodies like 1, separase) [NCBI Gene 315330], Aurkb (aurora kinase B) [NCBI Gene 114592] {aka ARK-2, Aim1, STK-1, Stk12}, Cenpw (centromere protein W) [NCBI Gene 689399] {aka CENP-W}, Cdca8 (cell division cycle associated 8) [NCBI Gene 500545], Kif2c (kinesin family member 2C) [NCBI Gene 171529] {aka KRP2, MCAK}, Asf1b (anti-silencing function 1B histone chaperone) [NCBI Gene 304648], Plk4 (polo-like kinase 4) [NCBI Gene 310344], Ncapg (non-SMC condensin I complex, subunit G) [NCBI Gene 305392] {aka RGD1562646}, Kif18a (kinesin family member 18A) [NCBI Gene 362186] {aka RGD1561740}, Cenpu (centromere protein U) [NCBI Gene 306464] {aka Mlf1ip}, Mtor (mechanistic target of rapamycin kinase) [NCBI Gene 56718] {aka Frap1, RAFT1}, Dlgap5 (DLG associated protein 5) [NCBI Gene 289997] {aka Dlg7}, Spag5 (sperm associated antigen 5) [NCBI Gene 252918] {aka Deepest}, Birc5 (baculoviral IAP repeat-containing 5) [NCBI Gene 64041] {aka AP14}, Nek2 (NIMA-related kinase 2) [NCBI Gene 114482], Cdc20 (cell division cycle 20) [NCBI Gene 64515] {aka p55cdc}, p53-ps (Wistar clone pR53P1 p53 pseudogene) [NCBI Gene 301300], Cdca2 (cell division cycle associated 2) [NCBI Gene 305984]
- **Diseases:** cardiovascular disorder (MESH:D002318), DVT (MESH:D020246)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116]

## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12256555/full.md

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Source: https://tomesphere.com/paper/PMC12256555