Exosome-transported circ_0001955 as a potent driver of breast cancer by regulating the miR-708-5p/PGK1 axis.

IF 2.3 3区医学 Q3 ONCOLOGY Thoracic Cancer Pub Date : 2024-10-29 DOI:10.1111/1759-7714.15479

Wenxin Li, Gaowa Jin, He Zhou, Yongqiang Gao, Yongli Ge, Huayi Zhang

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Abstract

Background: Increasing evidence shows that exosome-mediated delivery of circular RNA (circRNA) is implicated in breast cancer progression. This study aimed to elucidate the role of exosome-transported circ_0001955 in breast cancer.

Methods: The expression of circ_0001955, miR-708-5p, and phosphoglycerate kinase 1 (PGK1) messenger RNA (mRNA) was detected by quantitative real-time polymerase chain reaction (qRT-PCR); the protein levels of PGK1 and hexokinase 2 (HK2) were detected by western blot (WB). 5'-Ethynyl-2'-deoxyuridine (EdU) and colony formation assay were used to determine cell proliferation. Glycolytic metabolism was analyzed by corresponding kits to detect the associated indicators. The role of circ_0001955 in vivo was studied by establishing animal models. The potential binding relationship between miR-708-5p and circ_0001955 or PGK1 was verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay.

Results: Circ_0001955 was highly expressed in breast cancer tissues and cell lines, as well as in exosomes from breast cancer cell lines. The deficiency of circ_0001955 blocked proliferation, decreased the IC50 value of paclitaxel (PTX), and blocked glycolysis in MCF-7 and MDA-MB-231 cells. Circ_0001955 knockdown also inhibited tumor growth in vivo. Circ_0001955 directly combined with miR-708-5p, and the miR-708-5p inhibitor reversed the effects of sh-circ_0001955. PGK1 was a target of miR-708-5p, and circ_0001955 indirectly promoted PGK1 expression by binding to miR-708-5p. PGK1 overexpression abolished the function of miR-708-5p in breast cancer.

Conclusion: Exosomal circ_0001955 excreted from breast cancer cells facilitated proliferation and glycolysis and enhanced the IC50 value of PTX in breast cancer cells by sponging miR-708-5p to upregulate PGK1.

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外泌体转运的circ_0001955通过调节miR-708-5p/PGK1轴成为乳腺癌的强力驱动因素。

背景：越来越多的证据表明，外泌体介导的环状RNA（circRNA）传递与乳腺癌的进展有关。本研究旨在阐明外泌体转运的 circ_0001955 在乳腺癌中的作用：方法：采用实时定量聚合酶链反应（qRT-PCR）检测circ_0001955、miR-708-5p和磷酸甘油酸激酶1（PGK1）信使RNA（mRNA）的表达；采用免疫印迹（WB）检测PGK1和己糖激酶2（HK2）的蛋白水平。5'-乙炔基-2'-脱氧尿苷（EdU）和集落形成试验用于测定细胞增殖。用相应的试剂盒检测相关指标，分析糖酵解代谢。通过建立动物模型研究了 circ_0001955 在体内的作用。通过双荧光素酶报告实验和 RNA 免疫沉淀（RIP）实验验证了 miR-708-5p 与 circ_0001955 或 PGK1 之间的潜在结合关系：结果：circ_0001955在乳腺癌组织和细胞系以及乳腺癌细胞系的外泌体中高表达。缺乏 circ_0001955 会阻断 MCF-7 和 MDA-MB-231 细胞的增殖，降低紫杉醇（PTX）的 IC50 值，并阻断糖酵解。敲除 Circ_0001955 还能抑制体内肿瘤的生长。Circ_0001955直接与miR-708-5p结合，而miR-708-5p抑制剂能逆转sh-circ_0001955的作用。PGK1是miR-708-5p的靶标，circ_0001955通过与miR-708-5p结合间接促进了PGK1的表达。PGK1的过表达会削弱miR-708-5p在乳腺癌中的功能：结论：乳腺癌细胞排出的外泌体circ_0001955通过与miR-708-5p结合上调PGK1，促进了乳腺癌细胞的增殖和糖酵解，并提高了PTX在乳腺癌细胞中的IC50值。

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来源期刊

Thoracic Cancer ONCOLOGY-RESPIRATORY SYSTEM

CiteScore

5.20

自引率

3.40%

发文量

439

审稿时长

2 months

期刊介绍： Thoracic Cancer aims to facilitate international collaboration and exchange of comprehensive and cutting-edge information on basic, translational, and applied clinical research in lung cancer, esophageal cancer, mediastinal cancer, breast cancer and other thoracic malignancies. Prevention, treatment and research relevant to Asia-Pacific is a focus area, but submissions from all regions are welcomed. The editors encourage contributions relevant to prevention, general thoracic surgery, medical oncology, radiology, radiation medicine, pathology, basic cancer research, as well as epidemiological and translational studies in thoracic cancer. Thoracic Cancer is the official publication of the Chinese Society of Lung Cancer, International Chinese Society of Thoracic Surgery and is endorsed by the Korean Association for the Study of Lung Cancer and the Hong Kong Cancer Therapy Society. The Journal publishes a range of article types including: Editorials, Invited Reviews, Mini Reviews, Original Articles, Clinical Guidelines, Technological Notes, Imaging in thoracic cancer, Meeting Reports, Case Reports, Letters to the Editor, Commentaries, and Brief Reports.