Abstract
Background: Gastric cancer (GC) is a malignant tumor of the digestive tract. Hypoxia plays an important role in the development of cancer, including GC. The present study aimed to investigate the role of circular RNA SLAMF6 (circSLAMF6) in the progression of GC under hypoxia.Methods: The expression of circSLAMF6, microRNA-204-5p (miR-204-5p) and myosin heavy chain 9 (MYH9) was measured by quantitative real-time polymerase chain reaction (qRT-PCR). GC cells were maintained under hypoxia (1% O2) for experiments in vitro. Glucose consumption and lactate production were determined by a Glucose Assay Kit and a Lactate Assay Kit, respectively. Levels of all protein were detected by Western blot. Cell migration and invasion were examined by Transwell assay. The interaction between miR-204-5p and circSLAMF6 or MYH9 was analyzed by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Murine xenograft model was established to explore the role of circSLAMF6 in vivo.Results: CircSLAMF6 expression was increased in GC cells under hypoxia. Hypoxia promoted glycolysis, migration, and invasion in GC cells, which were reversed by circSLAMF6 knockdown. CircSLAMF6 was validated as a miR-204-5p sponge, and MYH9 was a target of miR-204-5p. Functionally, miR-204-5p inhibitor weakened the inhibition of circSLAMF6 knockdown on GC cell progression under hypoxia. Besides, MYH9 depletion suppressed glycolysis, migration, and invasion in GC cells under hypoxia. Importantly, circSLAMF6 deficiency inhibited tumor growth in vivo by regulating the miR-204-5p/MYH9 axis.Conclusion: CircSLAMF6 was involved in glycolysis, migration, and invasion by regulating the miR-204-5p/MYH9 axis in GC cells under hypoxia.
Highlights
Gastric cancer (GC) is a common malignancy, with more than 750000 additional cases annually worldwide [1]
The results indicated that the expression of circSLAMF6 was progressively induced in AGS and MKN-45 cells after exposure of hypoxia in a time dependent manner (Figure 1E,F)
These results demonstrated that circSLAMF6 might implicate in GC progression
Summary
Gastric cancer (GC) is a common malignancy, with more than 750000 additional cases annually worldwide [1]. Hypoxia has been shown to play an important role in the development of solid tumors, which accelerates the spread of tumors, malignant progression, and increases the resistance to chemotherapy [3,4]. Hypoxia plays an important role in the development of cancer, including GC. Cell migration and invasion were examined by Transwell assay. Migration, and invasion in GC cells, which were reversed by circSLAMF6 knockdown. MiR-204-5p inhibitor weakened the inhibition of circSLAMF6 knockdown on GC cell progression under hypoxia. MYH9 depletion suppressed glycolysis, migration, and invasion in GC cells under hypoxia. CircSLAMF6 deficiency inhibited tumor growth in vivo by regulating the miR-204-5p/MYH9 axis. Conclusion: CircSLAMF6 was involved in glycolysis, migration, and invasion by regulating the miR-204-5p/MYH9 axis in GC cells under hypoxia
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