Hsa_circ_0087784 enhances non-small cell lung cancer progression via the miR-576-5p/CDCA4 axis.

Bin Shang, Long Li, Gang Wang, Gang Liu, Xiaosong Yang, Jian Gao, Weiwei Yin
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Abstract

Background: Circular RNAs (circRNAs) belong to a family of covalently closed single-stranded RNAs that have been implicated in cancer progression. Previous studies have reported that hsa_circ_0087784 was abnormally expressed in breast cancer. However, the role of hsa_circ_0087784 in non-small cell lung cancer (NSCLC) is unknown.

Methods: Here, we used RT-qPCR and FISH to examine hsa_circ_0087784 expression in NSCLC cells and tissue samples. The dual-luciferase reporter assay was used to identify downstream targets of hsa_circ_0087784. Transwell migration, 5-ethynyl-2´-deoxyuridine, and CCK-8 assays were used to examine migration and proliferation. Tumorigenesis and metastasis assays were used to determine the role of hsa_circ_0087784 in NSCLC progression in a mouse tumor xenograft model in vivo.

Results: We found that hsa_circ_0087784 was expressed at significantly high levels in NSCLC tissue samples and cell lines. Downregulation of hsa_circ_0087784 suppressed NSCLC cellular proliferation, as well as migration. Our dual-luciferase reporter assay revealed that miR-576-5p and CDCA4 were downstream targets of hsa_circ_0087784. CDCA4 overexpression or miR-576-5p suppression reversed the effects of hsa_circ_0087784 silencing on NSCLC cell migration, and EMT-related protein expression levels.

Conclusion: Our findings suggested that downregulation of hsa_circ_0087784 inhibited NSCLC metastasis and progression through the regulation of CDCA4 expression and miR-576-5psponging.

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Hsa_circ_0087784 通过 miR-576-5p/CDCA4 轴增强小细胞肺癌的进展。
背景:环状 RNA(circRNA)属于共价封闭的单链 RNA 家族,与癌症进展有关联。以前的研究曾报道 hsa_circ_0087784 在乳腺癌中异常表达。方法:我们使用 RT-qPCR 和 FISH 检测了 hsa_circ_0087784 在 NSCLC 细胞和组织样本中的表达。方法:我们采用 RT-qPCR 和 FISH 方法检测了 hsa_circ_0087784 在 NSCLC 细胞和组织样本中的表达,并使用双荧光素酶报告实验确定了 hsa_circ_0087784 的下游靶标。Transwell迁移、5-乙炔基-2´-脱氧尿苷和CCK-8试验用于检测迁移和增殖。肿瘤发生和转移试验用于确定 hsa_circ_0087784 在小鼠体内肿瘤异种移植模型中对 NSCLC 进展的作用:结果:我们发现,hsa_circ_0087784在NSCLC组织样本和细胞系中的表达水平很高。下调 hsa_circ_0087784 可抑制 NSCLC 细胞的增殖和迁移。我们的双荧光素酶报告实验发现,miR-576-5p 和 CDCA4 是 hsa_circ_0087784 的下游靶标。CDCA4 的过表达或 miR-576-5p 的抑制逆转了 hsa_circ_0087784 沉默对 NSCLC 细胞迁移和 EMT 相关蛋白表达水平的影响:我们的研究结果表明,下调hsa_circ_0087784可通过调控CDCA4的表达和miR-576-5psonging抑制NSCLC的转移和进展。
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