# Preliminary Study of Differential circRNA Expression and Investigation of circRNA–miRNA–mRNA Competitive Endogenous Network in Rumen Acidosis of Holstein Cattle

## TL;DR

This study explores how circular RNAs may influence ruminal acidosis in cows, revealing a network of RNA interactions that could help improve cattle health and productivity.

## Contribution

The study presents the first circRNA expression profile and ceRNA network in subacute rumen acidosis of Holstein cattle.

## Key findings

- 65 differentially expressed circRNAs were identified in sick versus healthy cows.
- A ceRNA network involving 57 circRNAs, 14 miRNAs, and 22 mRNAs was constructed.
- Key pathways like NF-kappa B and TNF signaling were linked to inflammation in ruminal acidosis.

## Abstract

High-grain diets can make cows sick with ruminal acidosis, a digestive problem that reduces their health and productivity. Our study aimed to discover how special molecules, called circular RNAs, might affect this illness. In six Holstein cows, we found 65 distinct circular RNAs that change between healthy and sick animals, along with a web of connections to other body molecules. This shows these molecules likely influence ruminal acidosis. Such findings could guide farmers to prevent this disorder, improving cow well-being and boosting dairy and beef benefits for society.

Rumen acidosis is a widespread digestive disorder in livestock, causing inflammation and lowering animal performance. Unraveling its molecular mechanisms is vital for improving cattle health and welfare. Circular RNAs (circRNAs) are noncoding RNAs functioning as miRNA or protein sponges. This study employed high-throughput RNA sequencing to identify differentially expressed (DE) circRNAs in subacute rumen acidosis (SARA) in Holstein cattle, revealing 65 DE-circRNAs. We constructed a competitive endogenous RNA (ceRNA) network comprising 57 circRNAs, 14 miRNAs, and 22 mRNAs. Key hub nodes included circRNAs (8:69996068-69996853, 16:2614111-2615445, 5:109525933-109531380, 20:63115665-63116774), miRNAs (bta-miR-146b, bta-miR-181a, bta-miR-223, bta-miR-130b), and mRNAs (SLC2A3, SOCS3, DLC1, ARRDC4). Examination of hub circRNA host genes identified 30 DE transcription factors (TFs). Functional and pathway enrichment analysis pinpointed inflammation and immune response pathways, such as NF-kappa B and TNF signaling. This pioneering study offers the first circRNA expression profile and ceRNA network in SARA cattle, indicating circRNAs’ role in inflammation regulation, thus enhancing our understanding of SARA’s systems biology and potential treatment strategies.