Down-regulating circular RNA_0004674 delays the progression of oral squamous cell carcinoma through microRNA-377-3p/THBS1 axis.

Life sciences(2021)

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摘要
OBJECTIVE:Circular RNAs (CircRNAs) are of great significance in oral squamous cell carcinoma (OSCC) cell progression. Insufficiently, the performance of Circ_0004674 has not been specified in the disease, which alighted our desire to unmask its actions in OSCC cell progression with microRNA (miR)-377-3p and thrombospondin-1 (THBS1). METHODS:OSCC expression chip were collected through GEO database and analyzed. The upstream mechanism of THBS1 was predicted through databases. OSCC cancer tissues and normal tissues were resected, in which Circ_0004674, miR-377-3p and THBS1 expression were examined. The relationship of Circ_0004674, miR-377-3p and THBS1 was identified. Circ_0004674- and/or miR-377-3p-related oligonucleotides were transfected into CAL27 cells for detecting cell biological behaviors. Tumors in mice were implanted to monitor the tumor-forming ability of cells. RESULTS:THBS1 showed high expression in the three OSCC chips, and it was enriched in PI3K-AKT signaling pathway. The upstream mechanism of THBS1 predicted that Circ_0004674 regulated THBS1 through miR-377-3p. Circ_0004674 and THBS1 levels were enhanced while miR-377-3p level was reduced in OSCC. Down-regulating Circ_0004674 restricted the growth of CAL27 cells in vivo and in vitro. Restoring miR-377-3p, the target gene of Circ_0004674, destroyed CAL27 cell progression and tumor growth. miR-377-3p suppression rescued the effects of down-regulated Circ_0004674 on OSCC. THBS1 was negatively mediated by miR-377-3p. CONCLUSION:It is clarified that depleting Circ_0004674 mediates miR-377-3p to restrain THBS1, after which OSCC cell progression can be suppressed. It widens the way to control OSCC from a novel perspective.
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关键词
Circular RNA_0004674,MicroRNA-377-3p,Oral squamous cell carcinoma,Thrombospondin-1,Tumor growth
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