CircSPIDR acts as a tumour suppressor in cervical adenocarcinoma by sponging miR-431-5p and regulating SORCS1 and CUBN expression.
CircSPIDR acts as a tumour suppressor in cervical adenocarcinoma by sponging miR-431-5p and regulating SORCS1 and CUBN expression.
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CircSPIDR通过海绵状转移miR-431- 5 p并调节SORCS 1和CUBN表达在宫颈腺癌中起肿瘤抑制作用。
DOI：
10.18632/aging.203283
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发表时间：
2021-07-29
期刊：
影响因子：
--
通讯作者：
Lu W
中科院分区：
文献类型：
--
作者：
Xu J;Lu W
为了确定具有肿瘤抑制活性的环状RNA(CircRNAs)对宫颈腺癌的抑制作用，我们比较了宫颈腺癌和正常宫颈组织的CircRNA水平。我们发现，在子宫颈腺癌组织中，CircSPIDR的表达显著下调。在宫颈癌细胞中，CircSPIDR的过表达降低了细胞活力，抑制了克隆形成，促进了细胞凋亡，而CircSPIDR的过表达则起到相反的作用。在异种移植小鼠模型中，CircSPIDR过表达也抑制了子宫腺癌细胞的致瘤性。CircSPIDR通过海绵结合miR-431-5P，从而抑制Sortin相关的VPS10结构域受体1(SORCS1)和Cubilin(CUBN)，从而抑制宫颈腺癌的发展。在临床宫颈组织中，CircSPIDR的表达与miR-431-5p的表达呈负相关，与SORCS1和CUBN的表达呈正相关。这些结果表明，CircSPIDR通过竞争性地与miR-431-5p结合，从而上调SORCS1和CUBN，从而抑制宫颈腺癌。这些发现表明，CircSPIDR可作为治疗宫颈腺癌患者的新靶点。
To identify circular RNAs (circRNAs) with tumor suppressor activity against cervical adenocarcinoma, we compared the circRNA levels of cervical adenocarcinoma and normal cervical tissues. We found that circSPIDR was dramatically downregulated in cervical adenocarcinoma tissues. In cervical adenocarcinoma cells, overexpression of circSPIDR reduced cell viability, inhibited colony formation and promoted apoptosis, whereas knockdown of circSPIDR exerted the opposite effects. CircSPIDR overexpression also suppressed the tumorigenicity of cervical adenocarcinoma cells in a xenograft mouse model. CircSPIDR was found to sponge miR-431-5p, thereby de-repressing sortin-related VPS10 domain-containing receptor 1 (SORCS1) and cubilin (CUBN) and inhibiting the development of cervical adenocarcinoma. In clinical cervical samples, circSPIDR expression correlated negatively with miR-431-5p expression and positively with SORCS1 and CUBN expression. These results demonstrated that circSPIDR suppresses cervical adenocarcinoma by competitively binding to miR-431-5p, thus upregulating SORCS1 and CUBN. These findings suggest circSPIDR could serve as a novel therapeutic target for treatment of cervical adenocarcinoma patients.
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