EIF4A3-regulated circ_0087429 can reverse EMT and inhibit the progression of cervical cancer via miR-5003-3p-dependent upregulation of OGN expression.
EIF4A3-regulated circ_0087429 can reverse EMT and inhibit the progression of cervical cancer via miR-5003-3p-dependent upregulation of OGN expression.
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DOI：
10.1186/s13046-022-02368-4
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发表时间：
2022-05-05
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环状RNAs(CircRNAs)是一类结构稳定、高表达和组织特异性表达的非编码RNA。研究表明，CircRNA的失调与肿瘤的进展密切相关。然而，大多数CircRNAs在宫颈癌中的功能和调控机制仍不清楚，通过基因表达总览(GEO)数据库筛选了与宫颈癌相关的CircRNAs。采用定量逆转录聚合酶链式反应(QRT-PCR法)检测CIRC0087429在宫颈癌组织和细胞中的表达。然后，通过体内和体外实验，评价CIRC_0087429在宫颈癌发生发展中的作用。通过挽救实验、荧光原位杂交、荧光素酶报告分析、免疫荧光染色和Western blotting，证实了CIRC_0087429/miR-5003-3p/OGN轴在上皮向间充质转化中的作用。真核细胞起始因子4A-III(EIF4A3)对CIRC_0087429的生物发生有抑制作用。CIRC_0087429在宫颈癌组织和细胞中的表达显著下调，并与国际妇产科联合会(FIGO)分期和宫颈癌患者的淋巴转移呈负相关。CIRC_0087429在体外能显著抑制宫颈癌的增殖、迁移、侵袭和血管生成，在体内能显著抑制肿瘤的生长和转移。OGN在宫颈癌组织和细胞中的表达显著下调。CIRC_0087429通过与miR-5003-3p竞争性结合，上调OGN的表达，从而逆转宫颈上皮间质转移，抑制宫颈癌的发展。EIF4A3可通过与其侧翼区域结合来抑制CIRC_0087429的表达。作为一种肿瘤抑制因子，受EIF4A3调控的CIRC_0087429可以通过miR-5003-3p/ogn轴逆转宫颈上皮细胞的转移，抑制宫颈癌的进展。它有望成为治疗宫颈癌的潜在靶点。网上版载有补充材料，可在10.1186/s13046-022-02368-4查阅。
Circular RNAs (circRNAs) are noncoding RNAs with stable structures with high expression and tissue-specific expression. Studies have shown that circRNA dysregulation is closely related to the progression of tumours. However, the function and regulatory mechanism of most circRNAs in cervical cancer are still unclear. CircRNAs related to cervical cancer were screened through the Gene Expression Omnibus (GEO) database. qRT-PCR was used to verify the expression of circ_0087429 in cervical cancer tissues and cells. Then, in vivo and in vitro experiments were conducted to evaluate the role of circ_0087429 in the progression of cervical cancer. The role of the circ_0087429/miR-5003-3p/osteoglycin (OGN) axis in the epithelial to mesenchymal transition (EMT) was confirmed by rescue experiments, fluorescence in situ hybridization, luciferase reporter assays, immunofluorescence staining and western blotting. The inhibitory effect of Eukaryotic initiation factor 4A-III (EIF4A3) on the biogenesis of circ_0087429 was verified by RNA immunoprecipitation (RIP) assays and qRT-PCR. circ_0087429 is significantly downregulated in cervical cancer tissues and cells and negatively correlated with International Federation of Gynecology and Obstetrics (FIGO) staging and lymphatic metastasis in cervical cancer patients. circ_0087429 can significantly inhibit the proliferation, migration, invasion and angiogenesis of cervical cancer in vitro and tumour growth and metastasis in vivo. OGN is significantly downregulated in cervical cancer tissues and cells. circ_0087429 can upregulate the expression of OGN by competitively binding with miR-5003-3p, thereby reversing EMT and inhibiting the progression of cervical cancer. EIF4A3 can inhibit circ_0087429 expression by binding to its flanking regions. As a tumour suppressor, circ_0087429 regulated by EIF4A3 can reverse EMT and inhibit the progression of cervical cancer through the miR-5003-3p/OGN axis. It is expected to become a potential target for the treatment of cervical cancer. The online version contains supplementary material available at 10.1186/s13046-022-02368-4.
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