circFIG 4 drives the carcinogenesis and metastasis of esophagus cancer via the miR‐493‐5p/E2F3 axis

Abstract

Background: Esophageal cancer (EC) is a highly malignant tumor of the digestive tract. Circular RNAs (circRNAs) have been verified to play a regulatory role in the occurrence and progression of different cancers, including EC. This research aimed to investigate the role and molecular mechanism of circFIG 4 in EC progression. Methods: The analyses of circFIG 4, miR-493-5p, and neuro-oncological ventral antigen 2 levels were administrated by quantitative real-time polymerase chain reaction. The characteristics of circFIG 4 were determined by Ribonuclease R assay and Actinomycin D assay. Cell proliferation was assessed via colony formation assay and 5-ethynyl-2 0deoxyuridine incorporation assay. Cell cycle distribution and apoptosis were evaluated by flow cytometry. Western blot was performed to assess protein expression. The targeted interaction among circFIG 4, miR-493-5p, and E2F transcription factor 3 (E2F3) were validated using dual-luciferase reporter or RNA immunoprecipitation assays. Results: circFIG 4 was overtly upregulated in EC and was relatively stable in EC cells. circFIG 4 knockdown impeded proliferation, migration, and invasion and expedited apoptosis in EC cells. circFIG 4 served as a miR-493-5p sponge to act in the development of EC. Furthermore, circFIG 4 modulated EC progression via targeting miR-493-5p and miR-493-5p suppressed EC progression via targeting E2F3. circFIG 4 modulated E2F3 expression through acting as a sponge of miR-493-5p. Moreover, circFIG 4 knockdown inhibited EC tumorigenesis by targeting miR-493-5p/E2F3 axis tumor growth in vivo. Conclusion: circFIG 4 silence mitigated EC malignant progression at least partly by mediating the miR-493-5p/E2F3 pathway, highlighting new biomarkers and therapeutic targets for EC treatment.

Cancer‐associated fibroblasts promote tumor cell growth via miR‐493‐5p in intrahepatic cholangiocarcinoma

“…Several studies have shown that miR‐493‐5p has antitumor functions in various cancer types. Although miR‐493‐5p has been reported to function in a suppressive manner in various cancer types, 27 , 28 , 29 it has not been reported in cholangiocarcinomas, including ICC. The expression patterns and biological mechanisms of miR‐493‐5p in ICC progression have not yet been fully elucidated.…”

MicroRNAs: A novel signature in the metastasis of esophageal squamous cell carcinoma

“…Not more than that, the same miRNA can be regulated by different epigenetic mechanisms. For example, miR-493-5p, is dramatically downregulated in ESCC tissues and cells due to “sponging” from both circFIG4 and linc00324, both of which modulated ESCC progression including ESCC cell invasion and migration via targeting the miR-493-5p/E2F3 and miR-493-5p/MAPK1 axis, respectively[ 145 - 147 ]. Another example, miR-124-3p, was found to have positive correlations with ESCC invasion and migration, as well as EMT via the regulation of lncZFAS1 and through DNA methylation[ 31 , 127 ].…”

Circular RNAs in Cell Cycle Regulation of Cancers

“…Normally found upregulated, circFIG4 promotes cell cycle activity through sponging miR-493-5p, releasing E2F3 from being repressed [ 124 ]. Interestingly, circFNDC3B and hsa_circ_00014879 (circDCAF8) positively influence the same downstream target, CDC25A.…”