Circ_0000527 promotes the progression of retinoblastoma by regulating miR-646/LRP6 axis.

Background: Researches validate that circular RNAs (circRNAs) are dysregulated in a variety of malignancies and play an important role in regulating the malignant phenotype of tumor cells. Nevertheless, the role of circ_0000527 in retinoblastoma (RB) and its regulatory mechanisms remain largely unknown.

Methods: Real-time PCR (RT-PCR) was used to detect circ_0000527 and miR-646 expression in RB tissues and cells. The LRP6 expression in RB cells was detected by Western blot. The relationship between circ_0000527 expression and the clinicopathological parameters of RB patients was analyzed. Cell proliferation, apoptosis and metastasis were monitored by cell counting kit-8 (CCK-8), flow cytometry, and Transwell assay. The dual-luciferase reporter gene assay and RIP assay were employed to verify the targeting relationship between circ_0000527 and miR-646, miR-646 and LRP6.

Results: Circ_0000527 was highly expressed in both RB and RB cell lines, whose high expression level and degree of differentiation were significantly correlated with the increase in cTNM staging level. Overexpression of circ_0000527 contributed to RB cell proliferation, migration, invasion and suppressed cell apoptosis, while knocking down circ_0000527 inhibited the above malignant biological behavior. The underlying mechanism suggested that functioning as a endogenous competitive RNA, circ_0000527 directly targeted miR-646 and positively regulated LRP6 expression.

Conclusion: Circ_0000527 enhances the proliferation and metastasis of RB cells by modulating the miR-646/LRP6 axis.