circ_0058063 promotes breast cancer progression by upregulating DLGAP5 via sponging miR-557.

IF 2.2 4区医学 Q3 ONCOLOGY

Cancer Biomarkers Pub Date : 2024-01-01 DOI:10.3233/CBM-220410

Kongjun Zhu, Cen Yi, Chuanming Tong

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引用次数: 0

Abstract

Objective: Accumulating evidence indicates that circular RNAs (circRNAs) contribute to breast cancer (BC) development and progression. However, the role of circ_0058063 in BC and its underlying molecular processes remain unclear.

Methods: The expression of circ_0058063, miR-557, and DLGAP5 in BC tissues and cells was determined using real time quantitative PCR or western blotting. The functions of circ_0058063 in BC cells were detected using CCK-8, Transwell, caspase-3 activity, and xenograft tumor assays. The specific binding of circ_0058063/miR-557 and DLGAP5/miR-557 was verified using RNA immunoprecipitation (RIP) and dual-luciferase reporter assays.

Results: circ_0058063 expression was upregulated in BC tissues and cells. circ_0058063 knockdown inhibited proliferation and migration but promoted apoptosis in MCF-7 and MDA-MB-231 cells in vitro. In vivo studies further validated that the knockdown of circ_0058063 repressed tumor growth. Mechanistically, circ_0058063 directly sponged miR-557 and negatively regulated its expression. Additionally, miR-557 inhibition reversed the tumor-suppressive effects of the circ_0058063 knockdown on the survival of MDA-MB-231 and MCF-7 cells. Moreover, miR-557 directly targeted DLGAP5. DLGAP5 knockdown suppressed MCF-7 and MDA-MB-231 cell growth, and these effects were reversed by miR-557 downregulation.

Conclusion: Our findings verify that circ_0058063 acts as a sponge for miR-557 to upregulate DLGAP5 expression. These findings suggest that the circ_0058063/miR-557/DLGAP5 axis is an important regulator of oncogenic function and may be a promising therapeutic target for BC.

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circ_0058063 通过海绵状 miR-557 上调 DLGAP5，从而促进乳腺癌的进展。

目的：越来越多的证据表明，环状 RNA（circRNA）有助于乳腺癌（BC）的发生和发展。然而，circ_0058063在乳腺癌中的作用及其潜在的分子过程仍不清楚：方法：采用实时定量 PCR 或 Western 印迹法测定 circ_0058063、miR-557 和 DLGAP5 在 BC 组织和细胞中的表达。利用 CCK-8、Transwell、caspase-3 活性和异种移植肿瘤试验检测了 circ_0058063 在 BC 细胞中的功能。结果：circ_0058063在BC组织和细胞中表达上调。体外研究发现，circ_0058063敲除抑制了MCF-7和MDA-MB-231细胞的增殖和迁移，但促进了细胞凋亡。体内研究进一步验证了circ_0058063的敲除抑制了肿瘤的生长。从机理上讲，circ_0058063 直接疏导 miR-557，并负向调节其表达。此外，抑制 miR-557 可逆转 circ_0058063 敲除对 MDA-MB-231 和 MCF-7 细胞存活率的抑制作用。此外，miR-557 直接靶向 DLGAP5。DLGAP5敲除抑制了MCF-7和MDA-MB-231细胞的生长，而这些效应被miR-557下调逆转：我们的研究结果验证了 circ_0058063 可作为 miR-557 的海绵，上调 DLGAP5 的表达。这些研究结果表明，circ_0058063/miR-557/DLGAP5 轴是致癌功能的一个重要调节因子，可能是治疗 BC 的一个有前景的靶点。

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来源期刊

Cancer Biomarkers ONCOLOGY-

CiteScore

5.20

自引率

3.20%

发文量

195

审稿时长

3 months

期刊介绍： Concentrating on molecular biomarkers in cancer research, Cancer Biomarkers publishes original research findings (and reviews solicited by the editor) on the subject of the identification of markers associated with the disease processes whether or not they are an integral part of the pathological lesion. The disease markers may include, but are not limited to, genomic, epigenomic, proteomics, cellular and morphologic, and genetic factors predisposing to the disease or indicating the occurrence of the disease. Manuscripts on these factors or biomarkers, either in altered forms, abnormal concentrations or with abnormal tissue distribution leading to disease causation will be accepted.