Circular RNA circHMCU promotes breast tumorigenesis through miR-4458/PGK1 regulatory cascade.

IF 2.7 3区生物学

Hereditas Pub Date : 2023-03-23 DOI:10.1186/s41065-023-00275-y

Shubian Qiu, Lele Zou, Ruimin Qiu, Xin Wang

{"title":"Circular RNA circHMCU promotes breast tumorigenesis through miR-4458/PGK1 regulatory cascade.","authors":"Shubian Qiu, Lele Zou, Ruimin Qiu, Xin Wang","doi":"10.1186/s41065-023-00275-y","DOIUrl":null,"url":null,"abstract":"Background: Circular RNAs (circRNAs) are abnormally expressed in breast cancer (BC). However, the biological function and mechanism of circHMCU still need to be further explored.Methods: The expression levels of circHMCU, miR-4458 and phosphoglycerate kinase 1 (PGK1) were measured by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. The glucose uptake, lactate production and ATP level were assayed by related commercial kits. Cell Counting Kit-8 (CCK8), 5'-ethynyl-2'-deoxyuridine (EdU) and flow cytometry assays were used to test cell proliferation and apoptosis, respectively. The migratory and invasive abilities were detected by transwell and wound-healing assays. The relationships among circHMCU, miR-4458 and PGK1 were verified by dual-luciferase reporter assay. The function of circHMCU in tumor growth was evaluated by animal studies.Results: CircHMCU was upregulated in BC tissues and cell lines, whereas miR-4458 was downregulated. For biological experiments, circHMCU knockdown inhibited cell proliferation, migration, glycolysis, while promoted cell apoptosis. CircHMCU bound miR-4458, and miR-4458 targeted PGK1. MiR-4458 inhibition reversed circHMCM knockdown-mediated effects on BC cell malignant behaviors. MiR-4458 overexpression suppressed cell glycolysis, proliferation, and metastasis and promoted apoptosis in BC cells through PGK1 upregulation. Additionally, circHMCU suppressed tumor growth in vivo.Conclusion: CircHMCU acted as an oncogenic factor by regulating the miR-4458/PGK1 axis in BC.","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":null,"pages":null},"PeriodicalIF":2.7000,"publicationDate":"2023-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10035165/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Hereditas","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1186/s41065-023-00275-y","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Circular RNAs (circRNAs) are abnormally expressed in breast cancer (BC). However, the biological function and mechanism of circHMCU still need to be further explored.

Methods: The expression levels of circHMCU, miR-4458 and phosphoglycerate kinase 1 (PGK1) were measured by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. The glucose uptake, lactate production and ATP level were assayed by related commercial kits. Cell Counting Kit-8 (CCK8), 5'-ethynyl-2'-deoxyuridine (EdU) and flow cytometry assays were used to test cell proliferation and apoptosis, respectively. The migratory and invasive abilities were detected by transwell and wound-healing assays. The relationships among circHMCU, miR-4458 and PGK1 were verified by dual-luciferase reporter assay. The function of circHMCU in tumor growth was evaluated by animal studies.

Results: CircHMCU was upregulated in BC tissues and cell lines, whereas miR-4458 was downregulated. For biological experiments, circHMCU knockdown inhibited cell proliferation, migration, glycolysis, while promoted cell apoptosis. CircHMCU bound miR-4458, and miR-4458 targeted PGK1. MiR-4458 inhibition reversed circHMCM knockdown-mediated effects on BC cell malignant behaviors. MiR-4458 overexpression suppressed cell glycolysis, proliferation, and metastasis and promoted apoptosis in BC cells through PGK1 upregulation. Additionally, circHMCU suppressed tumor growth in vivo.

Conclusion: CircHMCU acted as an oncogenic factor by regulating the miR-4458/PGK1 axis in BC.

查看原文本刊更多论文

环状RNA circHMCU通过miR-4458/PGK1调控级联促进乳腺肿瘤发生。

背景:环状rna (circRNAs)在乳腺癌(BC)中异常表达。然而，circHMCU的生物学功能和机制仍需进一步探索。方法:采用实时荧光定量聚合酶链式反应(qRT-PCR)或western blot检测circHMCU、miR-4458和磷酸甘油酸激酶1 (PGK1)的表达水平。葡萄糖摄取、乳酸生成和ATP水平用相关的商用试剂盒检测。细胞计数试剂盒-8 (CCK8)、5′-乙基-2′-脱氧尿苷(EdU)和流式细胞术分别检测细胞增殖和凋亡。通过transwell和创面愈合试验检测其迁移和侵袭能力。circHMCU、miR-4458和PGK1之间的关系通过双荧光素酶报告基因实验验证。通过动物实验评估circHMCU在肿瘤生长中的作用。结果:CircHMCU在BC组织和细胞系中上调，而miR-4458下调。在生物学实验中，circHMCU敲低抑制细胞增殖、迁移、糖酵解，同时促进细胞凋亡。CircHMCU结合miR-4458, miR-4458靶向PGK1。MiR-4458抑制逆转了circHMCM敲低介导的BC细胞恶性行为。MiR-4458过表达通过上调PGK1抑制细胞糖酵解、增殖和转移，促进BC细胞凋亡。此外，circHMCU在体内抑制肿瘤生长。结论:CircHMCU通过调节BC中miR-4458/PGK1轴发挥致癌作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Hereditas Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

3.80

自引率

3.70%

发文量

期刊介绍： For almost a century, Hereditas has published original cutting-edge research and reviews. As the Official journal of the Mendelian Society of Lund, the journal welcomes research from across all areas of genetics and genomics. Topics of interest include human and medical genetics, animal and plant genetics, microbial genetics, agriculture and bioinformatics.