Salidroside Curbs Gastric Cancer Metabolism by Targeting Citrate Transporter via miR-1343-3p

The study, published open access in the journal Cancer & Metabolism, reports that salidroside acts through a small regulatory RNA called miR-1343-3p, which directly targets and downregulates SLC25A1, a transporter that exports citrate from mitochondria.

The research team, led by Mingyuan Cao, Zhendong Zhang and colleagues with corresponding author Xiaoping Wang, began with transcriptome sequencing of MGC-803 gastric cancer cells before and after salidroside treatment. This revealed 44 differentially expressed microRNAs and 1,384 differentially expressed messenger RNAs. Among these, miR-1343-3p was significantly upregulated and behaved as a tumor-suppressive microRNA, while SLC25A1, a mitochondrial citrate transporter, was significantly downregulated.

To confirm the regulatory relationship, the investigators used three independent approaches: a dual-luciferase reporter assay, sequence alignment, and RNA immunoprecipitation. All three confirmed that miR-1343-3p directly targets SLC25A1. Quantitative PCR and Western blotting further showed that salidroside significantly increased miR-1343-3p expression while decreasing both the mRNA and protein levels of SLC25A1 in the treated cells.

The functional consequences centered on mitochondrial metabolism. When the researchers applied salidroside, overexpressed miR-1343-3p, or silenced SLC25A1 in MGC-803 and AGS cells, they observed the same metabolic cascade in all three cases: citrate accumulated inside mitochondria, mitochondrial membrane potential dropped, reactive oxygen species production rose, and levels of NADH, ATP, acetyl-CoA, free fatty acids, cholesterol and triglycerides all declined. Cell proliferation was significantly inhibited.

Conversely, when the team knocked down miR-1343-3p, the opposite pattern emerged, with metabolic activity and proliferation recovering. Salidroside treatment efficiently rescued these effects, supporting the model that the compound works largely through this microRNA-target axis. Mitochondrial morphology and function were examined using transmission electron microscopy and fluorescent probes, providing structural evidence alongside the biochemical measurements.

The findings extended to living animals. In a nude mouse xenograft model of gastric cancer, both salidroside administration and a miR-1343-3p agomir, a synthetic molecule designed to enhance microRNA activity, significantly reduced tumor volume and weight. Tumor tissues from the treated groups showed increased miR-1343-3p expression, decreased SLC25A1 expression, and lipid metabolic changes consistent with those observed in the cell experiments.

The study’s strength lies in its converging lines of evidence, from transcriptomics through molecular validation to functional assays and xenograft models. By linking a plant-derived compound to a specific microRNA and a specific metabolic transporter, the work sketches a coherent mechanism: salidroside upregulates miR-1343-3p, which suppresses SLC25A1, blocking mitochondrial citrate export and starving cancer cells of the lipid building blocks they need to grow.

Important limitations remain. The experiments were conducted in two gastric cancer cell lines and in mouse xenografts, not in human patients, and the article was shared early as a peer-reviewed accepted manuscript subject to further edits before the final version of record.

Nevertheless, the authors conclude that miR-1343-3p and SLC25A1 may be promising therapeutic targets for metabolic intervention in gastric cancer.

Subject of Research: Salidroside regulation of mitochondrial citrate export and lipid metabolism in gastric cancer cells via the microRNA miR-1343-3p and its target SLC25A1.

Article Title: Salidroside decreases lipid abundance, mitochondrial function, and expression of the mitochondrial citrate transporter SLC25A1 via miR-1343-3p in gastric cancer

Article References: Cao, M., Zhang, Z., Du, Y., Fang, J., & Wang, X. (2026). Salidroside decreases lipid abundance, mitochondrial function, and expression of the mitochondrial citrate transporter SLC25A1 via miR-1343-3p in gastric cancer. Cancer & Metabolism. https://doi.org/10.1186/s40170-026-00454-1

Image Credits: AI Generated

DOI: 10.1186/s40170-026-00454-1

Keywords: salidroside, gastric cancer, miR-1343-3p, SLC25A1, mitochondrial metabolism, citrate transporter, lipid abundance, tumor metabolism, xenograft model, microRNA, decreases, lipid