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Hsa_Circ_0000021 通过调节 miR-3940-3p/KPNA2 的表达促进宫颈癌的进展。

Hsa_Circ_0000021 Sponges miR-3940-3p/KPNA2 Expression to Promote Cervical Cancer Progression.

机构信息

Department of Gynecology and Obstetrics, General Hospital of Western Theater Command of the Chinese People's Liberation Army, No. 270 Rongdu Avenue, Jinniu District, Chengdu 610083, Sichuan, China.

出版信息

Curr Mol Pharmacol. 2024;17(1):e170223213775. doi: 10.2174/1874467216666230217151946.

Abstract

BACKGROUND

Circular RNAs (circRNAs) have a vital role in the occurrence of numerous cancers. However, its function and pattern of expression in cervical cancer (CC) remain unclear. This research aims to investigate the hsa_circ_000002's regulatory mechanism in CC.

METHODS

Hsa_circ_0000021, miR-3940-3p, and KPNA2 expression levels were estimated through qRT-PCR. Nuclear/cytoplasmic separation was conducted to find the subcellular location of hsa_circ_0000021. Western blot was done to estimate the levels of KPNA2 protein. CCK-8, BrdU, wound healing, transwell, and tumor xenograft assays were performed to study how hsa_circ_0000021/miR-3940-3P/KPNA2 function affect CC. Hsa_circ_0000021's targeting relationships with miR-3940-3p and KPNA2 were ascertained through RIP and luciferase experiments.

RESULTS

Hsa_circ_0000021 and KPNA2 were overexpressed and inversely associated with the levels of miR-3940-3p in CC. Knocking down either hsa_circ_0000021 or KPNA2 repressed the growth of CC tumors as well as the proliferation, invasion, and migration of CC cells. Silencing miR-3940-3p promoted the malignant proliferation of CC cells. Regarding its mechanism, hsa_circ_0000021 affected the malignant CC cell proliferation via the sponging of miR-3940-3p, which targeted KPNA2.

CONCLUSION

Hsa_circ_0000021 regulates the miR-3940-3p/KPNA2 axis to promote CC occurrence. This potentially is a novel target for CC treatment.

摘要

背景

环状 RNA(circRNAs)在许多癌症的发生中起着至关重要的作用。然而,其在宫颈癌(CC)中的功能和表达模式尚不清楚。本研究旨在探讨 hsa_circ_000002 在 CC 中的调控机制。

方法

通过 qRT-PCR 评估 hsa_circ_0000021、miR-3940-3p 和 KPNA2 的表达水平。进行核/浆分离以确定 hsa_circ_0000021 的亚细胞定位。通过 Western blot 估计 KPNA2 蛋白水平。进行 CCK-8、BrdU、划痕愈合、Transwell 和肿瘤异种移植实验,以研究 hsa_circ_0000021/miR-3940-3P/KPNA2 功能如何影响 CC。通过 RIP 和荧光素酶实验确定 hsa_circ_0000021 与 miR-3940-3p 和 KPNA2 的靶向关系。

结果

在 CC 中,hsa_circ_0000021 和 KPNA2 表达上调,与 miR-3940-3p 的水平呈负相关。敲低 hsa_circ_0000021 或 KPNA2 均抑制 CC 肿瘤的生长以及 CC 细胞的增殖、侵袭和迁移。沉默 miR-3940-3p 促进了 CC 细胞的恶性增殖。就其机制而言,hsa_circ_0000021 通过海绵吸附 miR-3940-3p 影响恶性 CC 细胞的增殖,而 miR-3940-3p 靶向 KPNA2。

结论

hsa_circ_0000021 通过调节 miR-3940-3p/KPNA2 轴促进 CC 的发生。这可能是 CC 治疗的新靶点。

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