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Circular RNA circSCMH1 regulates glycolysis to inhibit gastric cancer metastasis via miR-296-3p/HSPB7-GLUT3 axis
Yue Yang1, Qiushuang Wang2, Zhe Gong3
1Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, PR China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, PR China; Department of Medical Oncology, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, PR China.
Abstract:
Metastasis is main reason leading to gastric cancer (GC) caused death. GC metastasis is known to be associated with complex factors, of which circular RNAs (circRNAs) become hot molecules recently. How to effectively select key molecules participating in GC metastasis is still needing to be resolved. Through next-generation sequencing, metastasis-driven circRNAs were selected by comparing cancer and para-cancer tissues from GC patients with different metastasis tendency. The biological function of circSCMH1 was identified in vivo and in vitro. Through luciferase reporter system and functional rescue test, the downstream microRNA and target gene were identified. Glucose uptake, lactic acid production and ATP production were detected to estimate glycolysis level. Moreover, 110 GC samples were collected and following clinical association analysis was conducted. circSCMH1 showed significantly lower expression in high-metastasis GC. circSCMH1 could suppress glycolysis to inhibit GC proliferation and metastasis in vivo and in vitro, and played its biological function through miR-296-3p/HSPB7-GLUT3 axis. circSCMH1 showed closely association with GC lymph node metastasis and prognosis. circSCMH1 could inhibit gastric cancer metastasis through regulating glycolysis via miR-296-3p/HSPB7-GLUT3 axis. circSCMH1 could become potential biomarker for GC lymph node metastasis and even therapeutic target in the future.
Insights
Circular RNAs (circRNAs) like circSCMH1 are crucial in gastric cancer (GC) metastasis. Lower circSCMH1 expression correlates with higher metastasis, suggesting it as a potential therapeutic target for GC.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Gastric cancer (GC) metastasis is a primary cause of cancer-related mortality.
- Circular RNAs (circRNAs) are emerging as critical regulators in GC metastasis.
- Identifying key molecules involved in GC metastasis remains a challenge.
Purpose of the Study:
- To identify metastasis-driven circRNAs in gastric cancer.
- To elucidate the biological function and mechanism of circSCMH1 in GC metastasis.
- To investigate the clinical significance of circSCMH1 in GC patients.
Main Methods:
- Next-generation sequencing to identify metastasis-associated circRNAs.
- In vivo and in vitro experiments to determine circSCMH1 function.
- Luciferase reporter assays and functional rescue tests to identify molecular interactions.
- Glycolysis assays (glucose uptake, lactate, ATP production).
- Clinical association analysis in 110 GC samples.
Main Results:
- circSCMH1 expression was significantly lower in high-metastasis GC tissues.
- circSCMH1 suppressed GC proliferation and metastasis by inhibiting glycolysis.
- The mechanism involves the circSCMH1/miR-296-3p/HSPB7-GLUT3 axis.
- Lower circSCMH1 expression was associated with lymph node metastasis and poor prognosis.
Conclusions:
- circSCMH1 inhibits gastric cancer metastasis by regulating glycolysis via the miR-296-3p/HSPB7-GLUT3 pathway.
- circSCMH1 serves as a potential biomarker for GC lymph node metastasis.
- circSCMH1 represents a promising therapeutic target for gastric cancer.
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