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

다국어 초록 (Multilingual Abstract)

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.

다국어 초록 (Multilingual Abstract)

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.