EIF4A3 调控的 circ_0087429 通过 miR-5003-3p 依赖性上调 OGN 表达逆转 EMT 并抑制宫颈癌进展。
EIF4A3-regulated circ_0087429 can reverse EMT and inhibit the progression of cervical cancer via miR-5003-3p-dependent upregulation of OGN expression.
机构信息
Department of Gynecology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 200092, China.
Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620, China.
出版信息
J Exp Clin Cancer Res. 2022 May 5;41(1):165. doi: 10.1186/s13046-022-02368-4.
BACKGROUND
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. METHODS: 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.
RESULTS
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.
CONCLUSIONS
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.
背景
环状 RNA（circRNA）是一类具有稳定结构、高表达和组织特异性表达的非编码 RNA。研究表明，circRNA 失调与肿瘤的发生发展密切相关。然而，大多数环状 RNA 在宫颈癌中的功能和调控机制尚不清楚。
方法
通过基因表达综合数据库（GEO）筛选与宫颈癌相关的 circRNA。采用 qRT-PCR 验证 circ_0087429 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估 circ_0087429 在宫颈癌进展中的作用。通过挽救实验、荧光原位杂交、荧光素酶报告基因检测、免疫荧光染色和 Western blot 验证 circ_0087429/miR-5003-3p/osteoglycin（OGN）轴在 EMT 中的作用。通过 RNA 免疫沉淀（RIP）实验和 qRT-PCR 验证真核起始因子 4A-III（EIF4A3）对 circ_0087429 生物发生的抑制作用。
结果
circ_0087429 在宫颈癌组织和细胞中显著下调，与宫颈癌患者的国际妇产科联合会（FIGO）分期和淋巴转移呈负相关。circ_0087429 可显著抑制宫颈癌的体外增殖、迁移、侵袭和血管生成，以及体内肿瘤生长和转移。OGN 在宫颈癌组织和细胞中显著下调。circ_0087429 可通过竞争性结合 miR-5003-3p 而上调 OGN 的表达，从而逆转 EMT 并抑制宫颈癌的进展。EIF4A3 可通过结合其侧翼区域抑制 circ_0087429 的表达。
结论
作为一种肿瘤抑制因子，circ_0087429 受 EIF4A3 调控，可通过 miR-5003-3p/OGN 轴逆转 EMT 并抑制宫颈癌的进展。有望成为宫颈癌治疗的潜在靶点。
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