Abstract
An increasing number of studies have indicated that circular RNAs (circRNAs) participate in the progression of numerous tumors. However, the functions of circRNAs in glioblastoma (GBM) remain largely unknown. In this study, we focused on a novel circRNA (hsa_circRFX3_003) that was spliced from RFX3, which we named circRFX3. We confirmed that the expression of circRFX3 was substantially increased in GBM cell lines and clinical GBM tissues. The results of a series of overexpression and knockdown assays indicated that circRFX3 could boost the proliferation, invasion, and migration of GBM cells. By performing dual-luciferase reporter gene and RNA pull-down assays, we verified that circRFX3 could sponge microRNA-587 (miR-587) to exercise its function as a competing endogenous RNA (ceRNA) in the development of GBM. In addition, PDIA3 was proven to be a downstream target of miR-587 and to regulate the Wnt/β-catenin pathway. In conclusion, circRFX3 could act as a cancer-promoting circRNA to boost the development of GBM and regulate the miR-587/PDIA3/β-catenin axis. This study might provide a novel target for the treatment of GBM with molecular therapy.
Highlights
In the central nervous system, gliomas are the most common tumors, accounting for approximately 80% of intracranial tumors (Alexander and Cloughesy, 2017)
The expression level of circRFX3 was much higher in GBM tissues from clinical patients than in normal brain tissue around the tumor, and the expression level of circRFX3 predicted a worse prognosis in a group of 42 GBM cases (Figure 1C)
The circRFX3 levels were subsequently examined in four GBM cell lines and HA cell line and primary human astrocytes (PHA1 and PHA2) through qRTPCR
Summary
In the central nervous system, gliomas are the most common tumors, accounting for approximately 80% of intracranial tumors (Alexander and Cloughesy, 2017). Glioblastomas (GBMs), which account for half of gliomas, are the most malignant (Janjua et al, 2021). It is important to identify novel effective targets in the development of GBM (Goodall and Wickramasinghe, 2021). Circular RNA (circRNA) is a noncoding RNA (ncRNA) that is diffusely expressed in cells. As a number of studies have indicated, circRNAs can function as competing endogenous RNAs (ceRNAs) that sponge miRNAs or bind to proteins to regulate the biological behavior of cells (Thomson and Dinger, 2016). There is convincing evidence verifying that circRNA plays an essential role in tumor progression—for example, circHMGA2 can regulate the development of lung cancer cells through the miR-1236-3p/ ZEB1 axis (Yu et al, 2021a). Hsa_circ_0001666 can boost the development of thyroid carcinoma upregulation of ETV4 (Qi et al, 2021), and circHIPK3 can influence myoblast progression by
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