Circular RNA DGKB Promotes the Progression of Neuroblastoma by Targeting miR-873/GLI1 Axis

Abstract

Accumulated evidences suggested that circular RNAs (circRNA) played critical roles in tumorigenesis and progression. To our knowledge, no study reported the function of circular RNA DGKB (circDGKB, circRNA ID: hsa_circ_0133622) on progression of neuroblastoma (NB). Here, we showed that circDGKB was upregulated in NB tissues compared to the normal dorsal root ganglia. Moreover, the expression level of circDGKB was negatively correlated with the survival rate of NB patients. Mechanically, overexpression of circDGKB promoted the proliferation, migration, invasion, and tumorigenesis of NB cells and reduced cell apoptosis, and vice versa. In addition, qRT-PCR and/or Western blot results showed that circDGKB overexpression inhibited the expression level of miR-873 and enhanced GLI1 expression. Moreover, miR-873 functioned an opposite role to circDGKB and significantly weakened circDGKB role in promoting NB progression. Furthermore, GLI1 upregulation also rescued the miR-873 role in inhibiting NB progression. In conclusion, our work proved that circDGKB promoted NB progression via targeting miR-873/GLI1 axis in vitro and in vivo. Our study provided a new target for NB treatment and indicated that circDGKB could act as a novel diagnostic marker for NB.

LncRNAs and CircRNAs in cancer

“…By detecting and comparing the expression of circDGKB in blood samples from neuroblastoma patients and healthy subjects, the expression level of circDGKB was significantly increased in neuroblastoma patients. 300 Furthermore, the level of circDGKB had an essential clinical value in diagnosing neuroblastoma with an area under the curve (AUC) of 0.7778. The results of the Kaplan–Meier analysis showed that patients with a high level of circDGKB had lower survival rates.…”

Emerging Role and Mechanism of circRNAs in Pediatric Malignant Solid Tumors

“…Circ-DGKB (hsa_circ_0133,622) expression was upregulated in NB tissues compared to normal dorsal root ganglia and negatively correlated with survival in NB patients. Circ-DGKB overexpression promoted NB cell proliferation, migration, invasion, and tumorigenesis and reduced apoptosis, promoting NB progression by targeting the miR-873/GLI1 axis in vitro and in vivo ( Yang et al, 2020 ). Circ-CUX1 and PHF20 are upregulated in NB tissues and cells, while miR-338-3p expression is significantly decreased.…”

“…The subject operating characteristic (ROC) curve was applied to investigate the diagnostic value of circ-HMGCS1 in distinguishing HB tissue from normative tissue showing that circ-HMGCS1 had diagnostic value (Area Under Curve (AUC) = 0.8283), with high expression of circ-HMGCS1 predicting poor prognosis in HB patients by Kaplan-Meier survival curve analysis ( Zhen et al, 2019 ). The expression of circ-DGKB in blood was found to be of clinical importance in the diagnosis of NB by ROC analysis (AUC = 0.7778), with Kaplan-Meier analysis showing that patients with high levels of circ-DGKB expression had a lower survival rate ( Yang et al, 2020 ). Zhang et al divided NB patients into high and low circ-CUX1 expression groups according to the median value of circ-CUX1 expression for survival analysis revealing that high expression of circ-CUX1 in NB patients was associated with shorter survival times.…”

MiR-873-5p: A Potential Molecular Marker for Cancer Diagnosis and Prognosis

“…Hsa_circ_0000069 can sponge miR-873-5p, which can promote the expression of TUSC3, thereby promoting the proliferation, migration, and invasion of CC cells ( 133 ). In Neuroblastoma, circDGKB can sponge miR-873-5p to increase the expression of ZEB1 and GLI1, and promote the occurrence and development of cancer ( 134 ). circ-UMAD1 can sponge miR-873-5p, thereby up-regulating the expression of Galectin-3 and inducing lymphatic metastasis of PTC ( 135 ).…”