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Hsa_circ_0087784通过miR-576-5p/CDCA4轴促进非小细胞肺癌进展。

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

作者信息

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

机构信息

Department of Cardio-Thoracic Surgery, The Second Affiliated Hospital of Bengbu Medical University, #633 Longhua Road, Huaishang District, Bengbu 233000 Anhui, China.

Department of Cardio-Thoracic Surgery, The Second Affiliated Hospital of Bengbu Medical University, #633 Longhua Road, Huaishang District, Bengbu 233000 Anhui, China.

出版信息

Am J Med Sci. 2025 Mar;369(3):390-397. doi: 10.1016/j.amjms.2024.09.002. Epub 2024 Sep 13.

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-576-5p sponging.

摘要

背景

环状RNA(circRNAs)属于一类共价闭合的单链RNA,与癌症进展有关。先前的研究报道hsa_circ_0087784在乳腺癌中异常表达。然而,hsa_circ_0087784在非小细胞肺癌(NSCLC)中的作用尚不清楚。

方法

在此,我们使用RT-qPCR和FISH检测hsa_circ_0087784在NSCLC细胞和组织样本中的表达。双荧光素酶报告基因检测用于鉴定hsa_circ_0087784的下游靶点。Transwell迁移、5-乙炔基-2'-脱氧尿苷和CCK-8检测用于检测迁移和增殖。肿瘤发生和转移检测用于在体内小鼠肿瘤异种移植模型中确定hsa_circ_0087784在NSCLC进展中的作用。

结果

我们发现hsa_circ_0087784在NSCLC组织样本和细胞系中表达水平显著升高。hsa_circ_0087784的下调抑制了NSCLC细胞的增殖以及迁移。我们的双荧光素酶报告基因检测显示miR-576-5p和CDCA4是hsa_circ_0087784的下游靶点。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。

结论

我们的研究结果表明,hsa_circ_0087784的下调通过调节CDCA4表达和miR-576-5p海绵作用抑制了NSCLC的转移和进展。

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