Circular RNA (circRNA) molecules contain microRNA (miRNA) response elements that are able to competitively bind miRNAs as well as function as miRNA sponges within cells, which can reduce miRNA inhibition of target genes, thereby increasing their expression. TargetScan and miRanda bioinformatic tools were used to analyze the binding sites between genes. The relative levels of gene expression in tissues and cells were verified using quantitative reverse transcription‐polymerase chain reaction. Inhibition of cell proliferation was detected using a WST‐8 method. Cell invasion ability and migration ability were assessed using a Transwell migration assay and a scratch assay, respectively. The binding of miRNA and circRNA was detected using an RNA pull‐down assay. Bifluorescence reporter gene vectors were constructed to verify the binding of miRNA to messenger RNA. A tumor model of cervical cancer cell transplantation in mice was constructed to observe the effect of the genes on tumor growth. hsa_circ_0031288 and B‐cell CLL/lymphoma 6 (Bcl‐6) exhibited high expression in cervical cancer cells and tissue, while hsa‐miR‐139‐3p exhibited low expression. Reducing hsa_circ_0031288 and Bcl‐6 expression or increasing hsa‐miR‐139‐3p expression significantly inhibited the migration, invasion, proliferation, and growth of xenograft and HeLa cells. hsa_circ_0031288 had a regulatory effect on hsa‐miR‐139‐3p, and hsa‐miR‐139‐3p targeted the 3′ untranslated region of Bcl‐6. Reducing hsa_circ_0031288 expression promoted hsa‐miR‐139‐3p expression, while overexpressing miR‐139‐3p inhibited the transcription of Bcl‐6. In the cervical cancer HeLa cell line, the hsa_circ_0031288/hsa‐miR‐139‐3p/Bcl‐6 regulatory axis affects cell migration and proliferation, and its mechanism may involve hsa_circ_0031288 acting as a sponge for hsa‐miR‐139‐3p, thereby relieving the transcriptional inhibition of Bcl‐6. This suggests an approach for elucidating the pathogenesis of cervical cancer while offering new intervention targets for cervical cancer treatment.

中文翻译：

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Hsa_circ_0031288 / hsa-miR-139-3p / Bcl-6调节反馈电路影响宫颈癌HeLa细胞的侵袭和迁移。

环状RNA（circRNA）分子包含microRNA（miRNA）响应元件，这些元件能够竞争性结合miRNA，并在细胞内充当miRNA海绵，可减少对靶基因的miRNA抑制，从而增加其表达。使用TargetScan和miRanda生物信息学工具分析基因之间的结合位点。使用定量逆转录聚合酶链反应验证了组织和细胞中基因表达的相对水平。使用WST-8方法检测到细胞增殖抑制作用。分别使用Transwell迁移测定法和刮擦测定法评估细胞侵袭能力和迁移能力。使用RNA下拉测定法检测miRNA和circRNA的结合。构建双荧光报告基因载体以验证miRNA与信使RNA的结合。构建了小鼠宫颈癌细胞移植的肿瘤模型，以观察基因对肿瘤生长的影响。hsa_circ_0031288和B细胞CLL /淋巴瘤6（Bcl-6）在宫颈癌细胞和组织中高表达，而hsa-miR-139-3p低表达。减少hsa_circ_0031288和Bcl-6表达或增加hsa-miR-139-3p表达可显着抑制异种移植和HeLa细胞的迁移，侵袭，增殖和生长。hsa_circ_0031288对hsa-miR-139-3p具有调节作用，hsa-miR-139-3p靶向Bcl-6的3'非翻译区。降低hsa_circ_0031288表达可促进hsa‐miR‐139‐3p表达，而过表达miR‐139‐3p可抑制Bcl-6的转录。在子宫颈癌HeLa细胞系中，hsa_circ_0031288 / hsa‐miR‐139‐3p / Bcl‐6调节轴影响细胞迁移和增殖，其机制可能涉及hsa_circ_0031288充当hsa‐miR‐139‐3p的海绵，从而减轻Bcl-6的转录抑制。这提示了一种阐明子宫颈癌发病机理的方法，同时为子宫颈癌治疗提供了新的干预目标。