miR-148b inhibits glycolysis in gastric cancer through targeting SLC2A1
Xiangfu Ding1, Jingjing Liu2, Tianzhou Liu2
1Department of Thyroid Surgery, The Second Hospital of Jilin University, Changchun, 130041, China.
Abstract:
Although the molecular biology of GC has been well characterized, early diagnostic biomarkers and effective therapeutic options in gastric cancer are still under investigation. Here, we found that miR-148b expression decreased in human gastric cancer tissues compared with matched adjacent nontumor tissues by q-PCR analysis and in situ hybridization. Further investigation revealed that overexpression of miR-148b limited glycolysis including glucose consumption, lactate production in gastric cancer cell lines BGC-823 and MKN45. Bioinformatics prediction uncovered that a dedicated transporters solute carrier family 2 member 1 (SLC2A1), also called GLUT1, was the direct target of miR-148b. The target effects were further confirmed by luciferase assay and western blot analysis. Besides, a reverse correlation was observed between relative SLC2A1 and miR-148b expression in human GC tissues compared with matched adjacent nontumor tissues. Subsequently, SLC2A1 suppression by SLC2A1 siRNA or specific inhibitor restricted the reduced effects of glycolysis mediated by miR-148b while SLC2A1 overexpression abrogated the effect of miR-148b on glycolysis. Our findings provided new evidence of miR-148b in GC development through restraining glycolysis, highlighting the role of miR-148b as a new target for GC treatment.
Insights
MicroRNA-148b (miR-148b) acts as a tumor suppressor in gastric cancer (GC) by limiting glycolysis. Its reduced expression in GC tissues suggests miR-148b is a potential therapeutic target for gastric cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Gastric cancer (GC) molecular biology is known, yet early diagnostic biomarkers and effective therapies remain elusive.
- MicroRNAs (miRNAs) play crucial roles in cancer development and progression.
- Dysregulation of metabolic pathways, such as glycolysis, is a hallmark of cancer.
Purpose of the Study:
- To investigate the role of miR-148b in gastric cancer.
- To identify the molecular mechanisms by which miR-148b affects gastric cancer cells.
- To explore the potential of miR-148b as a therapeutic target for gastric cancer.
Main Methods:
- Quantitative PCR (q-PCR) and in situ hybridization to assess miR-148b expression.
- Glycolysis assays (glucose consumption, lactate production) in gastric cancer cell lines.
- Bioinformatics prediction, luciferase assays, and Western blot analysis to validate miR-148b targets.
- siRNA and inhibitor studies to investigate the role of SLC2A1/GLUT1.
Main Results:
- miR-148b expression was significantly decreased in human gastric cancer tissues compared to adjacent non-tumor tissues.
- Overexpression of miR-148b suppressed glycolysis in gastric cancer cell lines.
- Solute carrier family 2 member 1 (SLC2A1), also known as GLUT1, was identified as a direct target of miR-148b.
- A reverse correlation between miR-148b and SLC2A1 expression was observed in GC tissues.
- Modulation of SLC2A1 levels affected the impact of miR-148b on glycolysis.
Conclusions:
- miR-148b functions as a tumor suppressor in gastric cancer by inhibiting glycolysis.
- miR-148b targets SLC2A1/GLUT1, a key regulator of glucose uptake.
- These findings highlight miR-148b as a promising novel therapeutic target for gastric cancer.
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