<p>The Potential Tumor Promotional Role of circVAPA in Retinoblastoma via Regulating miR-615-3p and SMARCE1</p>

Abstract

Background: Growing evidence reveals that circular RNAs (circRNAs) play roles in cancer development. However, the effects and possible mechanisms of circRNAs in retinoblastoma (RB) are far from clear. Methods: circVAPA expression pattern was identified by RT-qPCR. circVAPA induced effects on RB cells were tested by CCK-8, clone forming, flow cytometry and transwell assays. Bioinformatics assay, rescue experiments and dual-luciferase tests were applied for mechanism exploration. Additionally, mouse models were established for in vivo assays. Results: circVAPA was upregulated in human RB specimen and RB cell lines, and was correlated with poor outcomes of Rb patients. Knockdown of circVAPA could suppress the malignant phenotypes of RB. Mechanistic experiments demonstrated that miR-615-3p could reverse the circVAPA induced effects on RB cells, and the downstream oncogene SMARCE1 was positively regulated by circVAPA via miR-615-3p. Further, in vivo analysis confirmed the findings. Conclusion: In summary, circVAPA promoted RB proliferation and metastasis by sponging miR-615-3p, thereby upregulating SMARCE1. CircVAPA was a potential biomarker for Rb therapy.

The emerging role of circular RNAs in common solid malignant tumors in children

“…After studying the mechanism, he found that miR-615-3p can reverse the RB cell effect induced by circVAPA, and circVAPA positively regulates the downstream oncogene SMARCE1 through miR-615-3p. In addition, in vivo nude mice tumor formation experiments confirmed this finding [ 40 ]. Xing et al found that the down-regulation of the circular RNA hsa_circ_0001649 indicates that the prognosis of retinoblastoma is poor, and it regulates cell proliferation and apoptosis through the AKT/mTOR signaling pathway [ 41 ].…”

Emerging Role of Circular RNAs in the Pathogenesis of Retinoblastoma

“…In addition, high expression of circ_0000527 and miR-1236-3p was significantly associated with advanced TNM stages, positive optic nerve invasion, and positive choroidal invasion in Rb patients [38]. Xu et al [36] found that the expression of circVAPA in Rb was closely related to tumor size, lymph node metastasis, and FIGO stage, and patients with a high expression level of circVAPA showed worse overall survival. In contrast, there are some circRNAs with low expression in Rb tissues.…”

“…Furthermore, TET1-has_circ_0093996 might play a role in RB pathogenesis via regulating the TET1-circ_0093996/miR-183-PDCD4 axis [28]. In this context, circ_0000034, circ_0000527, circ_0119412, circ_0075804, circVAPA, and circFAM158A are significantly upmodulated in RB cell lines and tissues, whereas circ_0001649, circMKLN1, and circ_TET1 are expressed at low levels [30][31][32][33][34][35][36][37]. The roles of circRNAs in Rb include cellular and molecular mechanisms.…”

“…Xu et al [36] found that the expression of circVAPA in Rb was closely related to tumor size, lymph node metastasis, and FIGO stage, and patients with a high expression level of circVAPA showed worse overall survival. In contrast, there are some circRNAs with low expression in Rb tissues.…”

Circular RNA in Retina: A Potential Biomarker and Therapeutic Target

“…They further found that circDHDDS act as sponge of miR-361-3p, which promoted the proliferation of RB by regulating the expression of downstream Wnt3a gene. Xu’s study showed that circVAPA also increased in RB samples and cells, promoted RB cell proliferation through miR-615-3p/SMARCE1 axis, while the overexpression of miR-615-3p could inhibit the effect of circVAPA on RB cell proliferation [42]. S-phase kinase-associated protein 2 (SKP2) plays an accelerating role in various cancers.…”