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Background <p>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.</p> Methods <p>High-throughput sequencing combined with bioinformatics analysis predicted significantly differentially expressed miRNAs and target mRNAs after salidroside treatment. RNA-binding protein immunoprecipitation (RIP) was used to verify miRNA interaction with its downstream target protein, while co-immunoprecipitation (Co-IP) was applied to confirm downstream target proteins interaction. The IC<sub>50</sub> 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.</p> Results <p>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.</p> Conclusion <p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月20日

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  • Xinrui Hou,
  • Zhendong Zhang,
  • Mingyuan Cao,
  • Yuxin Du,
  • Xiaoping Wang

摘要

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

High-throughput sequencing combined with bioinformatics analysis predicted significantly differentially expressed miRNAs and target mRNAs after salidroside treatment. RNA-binding protein immunoprecipitation (RIP) was used to verify miRNA interaction with its downstream target protein, while co-immunoprecipitation (Co-IP) was applied to confirm downstream target proteins interaction. The IC50 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.