Circ_0001686 knockdown suppresses tumorigenesis and enhances radiosensitivity in esophagus cancer through regulating miR-876-5p/SPIN1 axis.

BACKGROUND

Abnormal expression of circular RNAs (circRNAs) plays an important role in tumorigenesis and radiosensitivity of many cancers. Nevertheless, it is not clear whether circ_0001686 is associated with the development and radiosensitivity of esophagus cancer.

METHODS

Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression levels of circ_0001686, microRNA-876-5p (miR-876-5p) and spindlin 1 (SPIN1). Counting Kit-8 (CCK-8) assay, EdU assay, flow cytometry and transwell assay were applied to evaluate cell viability, cell proliferation, cell apoptosis and cell invasion capacities. Radiosensitivity was monitored by colony formation assay. The target relationship between miR-876-5p and circ_0001686 or SPIN1 was identified by dual-luciferase reporter assay. The protein level of SPIN1 was measured by western blot assay. Xenograft tumor models were used to analyze the influence of circ_0001686 on radiosensitivity and tumor growth in vivo.

RESULTS

The expression levels of circ_0001686 and SPIN1 were increased, while miR-876-5p was decreased in esophagus cancer tissues and cells. Interference of circ_0001686 constrained cell proliferation and invasion, but promoted cell apoptosis and radiosensitivity. Additionally, miR-876-5p was the target of circ_0001686 and miR-876-5p inhibition effectively ameliorated the impacts of circ_0001686 deficiency on tumorigenesis and radiosensitivity. Moreover, SPIN1 was a direct target of miR-876-5p and SPIN1 overexpression partially overturned the effects of miR-876-5p transfection on tumor progression and radiosensitivity. Importantly, circ_0001686 could sponge miR-876-5p to regulate SPIN1 expression. In addition, circ_0001686 silencing also constrained tumor growth and increased radiosensitivity in vivo.

CONCLUSION

Circ_0001686 contributed to the progression and radioresistance of esophagus cancer cells via regulating SPIN1 expression by targeting miR-876-5p, providing a new therapeutic target for improving the prognosis of esophagus cancer patients.