通过 MAPK 信号通路鉴定成釉细胞瘤中的 circ_0089153/miR-608/EGFR p53 轴。
Identification of circ_0089153/miR-608/EGFR p53 axis in ameloblastoma via MAPK signaling pathway.
机构信息
Department of Periodontics, School and Hospital of Stomatology, Liaoning Provincial Key Laboratory of Oral Diseases, China Medical University, Shenyang, China.
Department of Oral Histopathology, School and Hospital of Stomatology, Liaoning Provincial Key Laboratory of Oral Disease, China Medical University, Shenyang, China.
出版信息
Oral Dis. 2022 Apr;28(3):756-770. doi: 10.1111/odi.13788. Epub 2021 Feb 9.
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.
目的
本研究探讨了环状 RNA（circRNAs）在成釉细胞瘤（AB）发病机制中的作用，为未来的靶向治疗确定潜在的新靶点。
材料和方法
使用微阵列构建 AB 中的 circRNA 和 microRNA（miRNA）谱。验证了 6 个新的 circRNA，描绘了 circ-miRNA 网络。通过数据库筛选、miRNA 微阵列和验证的交叉比较筛选出 hsa-miR-608。通过荧光素酶报告基因检测验证 circ-miRNA 结合海绵。筛选下游 mRNAs。体外证实了 miRNA 和 mRNAs 之间的调节作用。建立基因互作网络和 circRNA-miRNA-mRNA 互作通路富集分析。
结果
选择并验证了 6 个差异表达的 circRNA。根据预测的 miRNAs 和通路，选择了 6 个相关的 miRNAs，筛选出 hsa-miR-608 并进行验证。验证了 hsa_circ_0089153/hsa-miR-608 结合海绵。下游基因互作网络显示 EGFR 和 p53 具有最强的共表达。体外转染结果证实了 miR-608 和 EGFR p53 的抑制功能。hsa_circ_0089153/hsa-miR-608/EGFR p53 互作通路富集分析证实了主要富集在 MAPK 及相关信号通路，调节 AB 进展的功能。
结论
鉴定了 6 个新的 circRNA。验证了 hsa_circ_0089153/hsa-miR-608 海绵作用，hsa-miR-608 下调 EGFR 和 p53，可能通过 MAPK 信号通路进一步调节细胞增殖、分化、凋亡和细胞周期过程。
Zotero 插件