Work

miR-1343-3p regulating OGDHL/PDHB-pyruvate glucose metabolic reprogramming against gastric cancer cell proliferation

Year: 2025

Type: article

Abstract: BACKGROUND: Gastric cancer (GC) is the main cause for cancer-related mortality in the world. Recent studies have confirmed that metabolic reprogramming plays a significant role in cancer progression. This study aims to further clarify the underlying mechanisms that the tumor suppressor miR-1343-3p exerts anti-gastric cancer effects via glucose metabolic reprogramming pathways. METHODS: of salidroside was determined by in vitro CCK-8 assay and colony formation experiment. qRT-PCR, Western blot, ELISA, and ATP detection were used to evaluate cancer cell proliferation, miRNA-mRNA expression and metabolite changes. Cancer cells were transfection with miR-1343-3p mimics or inhibitors, OGDHL-targeted siRNA (si-OGDHL), to verify the effects of salidroside against cancers. In vivo tumor-bearing nude mouse models after salidroside or miR-1343-3p agomir treatments were applied to analyze the targeted miRNA-mRNA molecules expression and metabolite changes. RESULTS: Bioinformatics confirmed that tumor suppressor miR-1343-3p down-regulated OGDHL expression, a key α-ketoglutarate dehydrogenase complex subunit of TCA cycle. Our findings first verified that OGDHL interacted with PDHB, a key pyruvate dehydrogenase E1-β subunit in gastric cancer. Both in vitro and in vivo experiments revealed that salidroside inhibited GC growth in a time and dose-dependent way through up-regulating tumor suppressor miR-1343-3p, down-regulating OGDHL expression, destabilizing PDHB protein homeostasis, reducing pyruvate oxidative decarboxylation, and decreasing acetyl-CoA and ATP production. CONCLUSION: Tumor suppressor miR-1343-3p inhibited gastric cancer cell proliferation by regulating OGDHL/PDHB-pyruvate glucose metabolism axis, which lay a better basis for targeted therapeutic strategy in cancers.

Source: Discover Oncology

DOI: 10.1007/s12672-025-04298-x

Authors: Xinrui Hou, Zhendong Zhang, Mingyuan Cao, Yuxin Du, Xiaoping Wang

Institution: Xizang Minzu University

Language: English

Topic: MicroRNA in disease regulation

Subfield: Cancer Research

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $1,690