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Updated: Dec 11, 2025

MicroRNA-based Regulation of Picornavirus Tropism
Published on: February 6, 2017
SIDT1-dependent absorption in the stomach mediates host uptake of dietary and orally administered microRNAs
Qun Chen1, Fan Zhang1, Lei Dong1
1Nanjing Drum Tower Hospital Center of Molecular Diagnostic and Therapy, State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute of Life Sciences (NAILS), NJU Institute of AI Biomedicine and Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, 210023, China.
Abstract:
Dietary microRNAs have been shown to be absorbed by mammals and regulate host gene expression, but the absorption mechanism remains unknown. Here, we show that SIDT1 expressed on gastric pit cells in the stomach is required for the absorption of dietary microRNAs. SIDT1-deficient mice show reduced basal levels and impaired dynamic absorption of dietary microRNAs. Notably, we identified the stomach as the primary site for dietary microRNA absorption, which is dramatically attenuated in the stomachs of SIDT1-deficient mice. Mechanistic analyses revealed that the uptake of exogenous microRNAs by gastric pit cells is SIDT1 and low-pH dependent. Furthermore, oral administration of plant-derived miR2911 retards liver fibrosis, and this protective effect was abolished in SIDT1-deficient mice. Our findings reveal a major mechanism underlying the absorption of dietary microRNAs, uncover an unexpected role of the stomach and shed light on developing small RNA therapeutics by oral delivery.
Insights
Dietary microRNAs are absorbed in the stomach via SIDT1, a protein on gastric pit cells. This discovery explains how microRNAs enter the body and could lead to new oral small RNA therapies.
Area of Science:
- Molecular Biology
- Gastroenterology
- Genetics
Background:
- Dietary microRNAs can regulate host gene expression in mammals.
- The mechanism of dietary microRNA absorption remains largely unknown.
Purpose of the Study:
- To elucidate the mechanism of dietary microRNA absorption.
- To identify the primary site of dietary microRNA absorption.
- To investigate the role of SIDT1 in dietary microRNA uptake.
Main Methods:
- Utilized SIDT1-deficient mice to study microRNA absorption.
- Performed mechanistic analyses of exogenous microRNA uptake by gastric pit cells.
- Investigated the effect of plant-derived miR2911 on liver fibrosis in vivo.
Main Results:
- SIDT1 on gastric pit cells is essential for dietary microRNA absorption.
- The stomach is the primary site for dietary microRNA absorption.
- MicroRNA uptake by gastric pit cells is SIDT1 and low-pH dependent.
- Oral miR2911's protective effect against liver fibrosis is abolished in SIDT1-deficient mice.
Conclusions:
- SIDT1 mediates dietary microRNA absorption in the stomach.
- This study reveals a key mechanism for dietary microRNA uptake and identifies the stomach's crucial role.
- Findings support the development of oral small RNA therapeutics.
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