Identification of circ_0089153/miR‐608/EGFR p53 axis in ameloblastoma via MAPK signaling pathway

Abstract

Objectives: This study investigated the role of circular RNAs (circRNAs) in the pathogenesis of ameloblastoma (AB), identifying potential novel targets for future targeted therapy. Materials and Methods:CircRNA and microRNA (miRNA) profiling in AB were built with microarrays. Six novel circRNAs were validated, circ-miRNA networks were delineated. Hsa-miR-608 was filtered over cross-comparison between database screening, miRNA microarray and validated. Circ-miRNA binding sponge was validated via luciferase reporter assay. Downstream mRNAs were screened. Regulation between miRNAs and mRNAs was confirmed in vitro. Gene interaction networks and circRNA-miRNA-mRNA interaction pathway enrichment analyses were established.Results: Six differentially expressed circRNAs were selected and validated. According to miRNAs and pathways predicted, six correlated miRNAs were selected, hsa-miR-608 was filtered and validated. The hsa_circ_0089153/hsa-miR-608 binding sponge was validated. Downstream gene interaction networks showed that EGFR and p53 had the strongest co-expression. In vitro transfection results confirmed the suppressive function of miR-608 and EGFR p53. Hsa_circ_0089153/hsa-miR-608/ EGFR p53 interaction pathway enrichment analysis confirmed functions mainly enriched in MAPK and related signaling pathways regulating AB progression.Conclusions: Six novel circRNAs were identified. Hsa_circ_0089153/hsa-miR-608 sponging was validated, hsa-miR-608 downregulated EGFR and p53, which might further regulate cell proliferation, differentiation, apoptosis, and cell cycle processes via the MAPK signaling pathway.

Circular RNA circ_0089153 acts as a competing endogenous RNA to regulate colorectal cancer development by the miR-198/SUMO-specific peptidase 1 (SENP1) axis

“…Our results showed that circ_0089153 is overexpressed in colorectal primary tumors and CRC cells. In agreement with our findings, dysregulation of circ_0089153 has been reported in ameloblastoma and breast cancer [ 40 , 41 ]. Moreover, Li et al .…”

“…Our results showed that circ_0089153 is overexpressed in colorectal primary tumors and CRC cells. In agreement with our findings, dysregulation of circ_0089153 has been reported in ameloblastoma and breast cancer [40,41]. Moreover, Li et al uncovered that circ_0089153 functioned as an oncogenic driver in papillary thyroid cancer by sponging miR-145 to induce E-box binding homeobox 2 (ZEB2) expression [42].…”

Biological Functions and Molecular Mechanisms of MiR-608 in Cancer

“…For example, toosendanin (TSN) upregulates miR-608 and inhibits downstream targets, including Notch1 and Notch2 (41). In addition, circRNAs can also interact with miR-608, and Liu et al (42) revealed that a circ_0089153/miR-608/ EGFR/p53 interaction pathway exists in ameloblastoma (AB). The biological function of circ_0089153 relies on the MAPK signaling pathway (42).…”

“…Among these transmembrane proteins, EGFR is especially important because EGFR can interact with epidermal growth factor (EGF) and induce receptor dimerization and tyrosine autophosphorylation, resulting in cell proliferation. Both Liu et al (42) and Zhang et al (17) reported that EGFR is a target of miR-608 and that miR-608 can indirectly attenuate cell proliferation by inhibiting EGFR. Moreover, MMP-15, another transmembrane protein, binds to miR-608 and participates in the progression of AML.…”

“…Both Liu et al. ( 42 ) and Zhang et al. ( 17 ) reported that EGFR is a target of miR-608 and that miR-608 can indirectly attenuate cell proliferation by inhibiting EGFR.…”