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Background

Gastric cancer (GC) is the third leading cause of cancer-related deaths worldwide. MicroRNAs (miRNAs) have been widely validated as potential biomarkers for cancer treatment and diagnosis.

Aims

This paper intends to study the effect and specific mechanism of miR-574-3p/CUL2 axis in GC.

Methods

The miR-574-3p expression in GC tissues and cell lines was analyzed by reverse transcription polymerase chain reaction (RT-PCR). GC cell (N87) proliferation, migration and invasion were determined by the Brdu assay and Transwell assay, respectively. The tumor xenotransplantation model was established in vivo to test the effect of miR-574-3p or Cullin 2 (CUL2) on tumor growth. The relationship between miR-574-3p and CUL2 was predicated by bioinformatic analysis and verified by dual-luciferase reporter assay and RIP experiment. The expression of CUL2, hypoxia-induced transcription factor-1α (HIF-1α) as well as E-cadherin, Snail and Vimentin was monitored by western blot and immunohistochemistry.

Results

miR-574-3p was overexpressed in GC tissues and cells. Forced upregulation of miR-574-3p enhanced proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) of GC cells (N87), while downregulation of miR-574-3p resulted in reverse effects. Additionally, miR-574-3p promoted N87 cells growth and EMT in vivo. CUL2 was negatively regulated by miR-574-3p in N87 cells, and upregulation of CUL2 repressed the malignant behaviors of N87 cells. Moreover, CUL2 directly interacted with HIF-1α and suppressed HIF-1α expression both in vitro and in vivo.

Conclusions

miR-574-3p targeted CUL2 to upregulate HIF-1α, thus facilitating the progression of GC."xsd:string
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http://purl.uniprot.org/citations/34655362http://purl.uniprot.org/core/author"Liu Y."xsd:string
http://purl.uniprot.org/citations/34655362http://purl.uniprot.org/core/author"Sun J."xsd:string
http://purl.uniprot.org/citations/34655362http://purl.uniprot.org/core/author"Wang X."xsd:string
http://purl.uniprot.org/citations/34655362http://purl.uniprot.org/core/author"Zhong M."xsd:string
http://purl.uniprot.org/citations/34655362http://purl.uniprot.org/core/author"Shang J."xsd:string
http://purl.uniprot.org/citations/34655362http://purl.uniprot.org/core/date"2022"xsd:gYear
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http://purl.uniprot.org/citations/34655362http://purl.uniprot.org/core/title"MicroRNA-574-3p Regulates HIF-alpha Isoforms Promoting Gastric Cancer Epithelial-Mesenchymal Transition via Targeting CUL2."xsd:string
http://purl.uniprot.org/citations/34655362http://purl.uniprot.org/core/volume"67"xsd:string
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