Silencing circSLAMF6 represses cell glycolysis, migration, and invasion by regulating the miR-204-5p/MYH9 axis in gastric cancer under hypoxia

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.

MicroRNA-Based Risk Score for Predicting Tumor Progression Following Radioactive Iodine Ablation in Well-Differentiated Thyroid Cancer Patients: A Propensity-Score Matched Analysis

“…The predicted regulatory network showed that upregulated miR-221 and miR-222 and downregulated miR-204 leads to a subsequent cascade promoting thyroid cancer pathway ( Figure 7 ). A systematic review demonstrated multiple deregulated signaling pathways and mechanisms leading to tumor development ( Table S9 ) [ 28 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 ].…”

Depletion of hsa_circ_0000144 Suppresses Oxaliplatin Resistance of Gastric Cancer Cells by Regulating miR-502-5p/ADAM9 Axis

“…Hsa_circ_0000144 deficiency suppressed glycolysis, metastasis and tumorigenesis of GC cells under hypoxia through the regulation of miR-204-5p/MYH9 axis. 27 In addition, hsa_circ_0000144 sponged miR-623 to upregulate GPRC5A expression, so as to promote GC progression. 28 In keeping with former discoveries, we also detected the upregulation of hsa_circ_0000144 in GC tissues and cells, especially in OXA-resistant tissues and cells.…”

Circular versus linear RNA topology: different modes of RNA–RNA interactions in vitro and in human cells

“…Unlabelled dNTPs, DNase I, T7 RNA polymerase, Klenow fragment exo-, Klenow reaction buffer, RiboLock™, RNA size standards, and T4 polynucleotide kinase were purchased from ThermoFisher Scientific (Schwerte, Germany). Radioactively labelled ATP ([γ-[ 32 ]P]ATP) was obtained from PerkinElmer® (Groningen, Netherlands), T4 RNA Ligase I (T4 RnL) and the appropriate buffer from New England Biolabs (Frankfurt am Main, Germany). DNA primers were purchased from eurofins Genomics (Ebersberg, Germany), RNA oligonucleotides (21mers) were provided by IBA (Goettingen, Germany).…”