CircBUB1 activates the PI3K/AKT signaling pathway to promote the migration and invasion of glioblastoma cells

Glioblastoma (GBM), the most prevalent primary malignant brain tumor in adults, is characterized by aggressive and invasive nature. The standard therapy includes surgical resection accompanied with temozolomide chemotherapy and radiation treatment (Liu et al., 2021b; Ostrom et al., 2018). Nonetheless, the five-year survival rate is still below 5%, and the median survival time ranges from 12 to 15 months (Delgado-López and Corrales-García, 2016; Raj et al., 2020). Currently, GBM treatment remains technically challenging, primarily because therapy resistance and infiltrative pattern of tumor growth raise the risk of GBM recurrence (Chen et al., 2021b). The extensive inter- and intra-tumoral heterogeneity of GBM also complicates the development of new therapeutic strategies (Jacob et al., 2020). Therefore, it is necessary to enrich the knowledge of molecular mechanism in GBM and identify more therapeutic targets to improve GBM treatment.

Increasing evidence has suggested that circular RNAs (circRNAs), covalently closed RNA transcripts, highly engage in varied physiological and pathological processes (Gao et al., 2021; Wang et al., 2018). As reported by Chen et al., circPTK2 overexpression impedes the migration and invasion of GBM cells (Chen et al., 2021b). According to another research work, hsa_circ_0072309 is down-regulated in GBM and restrains the proliferation and invasion of GBM cells (Yuan et al., 2021). However, the expression patterns and biological roles of circRNAs in GBM still lack in-depth investigation.

CircRNAs have been revealed to serve as competing endogenous RNAs (ceRNAs) to sponge microRNAs (miRNAs), by which they are involved in diverse biological functions in cancers (Huang et al., 2020; Wang et al., 2020a). CeRNA networks connect the influence of protein-coding messenger RNAs (mRNAs) with that of non-coding RNAs, including circRNAs and miRNAs, at the post-transcription level (Qi et al., 2015). Published research work has also disclosed the involvement of ceRNA regulation in GBM. For instance, Liu et al. have confirmed that circCDC45 competes with CSF-1 for miR-485-5p, functionally exacerbating multiple malignant behaviors of GBM cells (Liu et al., 2021a). Additionally, the research work of Zhou et al. has pointed out circ_0001588 sequesters miR-211-5p to up-regulate YY1, thereby stimulating proliferation, migration, and invasion of GBM cells (Wang et al., 2021a).

This study focused on a novel circRNA which displayed the significantly differential expression in GBM tissues and adjacent normal tissues. Apart from the biological function of the identified circRNA in GBM cells, this study also tried to figure out its underlying mechanisms. The findings of this research might provide novel potential diagnosis biomarker for GBM.

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