Circ_0000277 promotes the malignant progression of oesophageal squamous cell carcinoma through miR-1294-dependent regulation of DVL3

Background

Recent studies have pinpointed that circular RNA (circRNA) regulates diverse cellular processes in oesophageal squamous cell carcinoma (ESCC). However, the role of circ_0000277 in ESCC progression remains unclear.

Methods

RNA levels of circ_0000277, microRNA-1294 (miR-1294) and dishevelled segment polarity protein 3 (DVL3) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Protein expression was analyzed by Western blotting analysis or immunohistochemistry assay. Cell viability and cell proliferation were investigated by a cell counting kit-8 assay and 5-Ethynyl-2’-deoxyuridine (EdU) assay. Cell migration and invasion were assessed by wound-healing assay and transwell invasion assay. Dual-luciferase reporter, RNA immunoprecipitation and RNA pull-down assays were conducted to identify the associations among circ_0000277, miR-1294 and DVL3. The xenograft mouse model assay was used to evaluate the effect of circ_0000277 on tumour’s tumorigenesis.

Results

Circ_0000277 and DVL3 expressions were significantly upregulated, while miR-1294 was downregulated in ESCC tissues and cells compared with control groups. Additionally, high expression of circ_0000277 was associated with poor prognosis of ESCC patients. Circ_0000277 overexpression promoted ESCC cell proliferation, migration and invasion; however, depletion of circ_0000277 displayed the opposite effects. Noticeably, circ_0000277 acted as a miR-1294 sponge, and regulated ESCC cell malignancy through interaction with miR-1294. DVL3 was identified as a target of miR-1294, and its overexpression attenuated miR-1294-induced effects in ESCC cells. Besides, circ_0000277 induced DVL3 expression by sponging miR-1294. Circ_0000277 knockdown suppressed tumour formation in vivo.

Conclusion

Circ_0000277 promoted ESCC malignant progression through the miR-1294/DVL3 pathway.

Highlights

1.

Circ_0000277 expression was upregulated in ESCC tissues and cells.

2.

Circ_0000277 contributed to ESCC cell proliferation, migration and invasion.

3.

Circ_0000277 induced DVL3 expression through sponging miR-1294.