MiRNA-145-5p Restrains Malignant Behaviors of Breast Cancer Cells Via Downregulating H2AFX Expression.

IF 1.6 4区生物学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Iranian Journal of Biotechnology Pub Date : 2023-07-01 DOI:10.30498/ijb.2023.349450.3433

Deshun Yao, Xin Chen

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引用次数: 0

Abstract

Breast cancer is a prevalent tumor with high aggressiveness among female populations. MiRNA-145-5p plays an important role in multiple cancers.

Materials and methods: qRT-PCR detected miRNA-145-5p and histone protein family member X (H2AFX) mRNA expression in breast cancer cells, and western blot determined the protein expression of H2AFX. After predicting the target genes via the bioinformatics methods, the targeting relationship between miRNA-145-5p and H2AFX was verified by dual-luciferase, RIP, and RNA pull-down assays. The relationship between H2AFX and clinical indexes was also analyzed. Furthermore, the effects of miRNA-145-5p/H2AFX regulatory axis on breast cancer cell progression were determined by colony formation, wound healing, CCK-8, and Transwell assays.

Results: The results suggested that miRNA-145-5p was markedly lowly-expressed in breast cancer tissue and cells, while H2AFX was upregulated, which had a positive correlation with T stages of breast cancer. Besides, overexpressed miRNA-145-5p was found to remarkably suppress progression of breast cancer cells. As bioinformatic analysis predicted that H2AFX was the potential target of miRNA-145-5p, the dual-luciferase assay was conducted, which demonstrated that miRNA-145-5p negatively regulated the expression of H2AFX by targeting its 3'-UTR. The rescue experiment demonstrated that overexpression of miRNA-145-5p could offset the promotion effects of oe-H2AFX on malignant progression.

Objective: Our study is aimed at exploring how miRNA-145-5p functions in breast cancer cells.

Conclusion: Our findings confirmed that miRNA-145-5p hindered malignant progression of breast cancer by negatively regulating H2AFX. MiRNA-145-5p/H2AFX axis may be a novel therapeutic target for breast cancer.

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MiRNA-145-5p 通过下调 H2AFX 表达抑制乳腺癌细胞的恶性行为

乳腺癌是女性人群中侵袭性很强的一种常见肿瘤。材料与方法：qRT-PCR检测乳腺癌细胞中miRNA-145-5p和组蛋白家族成员X（H2AFX）mRNA的表达，Western blot检测H2AFX的蛋白表达。通过生物信息学方法预测靶基因后，用双荧光素酶、RIP和RNA牵引实验验证了miRNA-145-5p与H2AFX的靶向关系。还分析了 H2AFX 与临床指标的关系。此外，miRNA-145-5p/H2AFX 调控轴对乳腺癌细胞进展的影响还通过集落形成、伤口愈合、CCK-8 和 Transwell 试验进行了测定：结果表明，miRNA-145-5p在乳腺癌组织和细胞中明显低表达，而H2AFX则上调，这与乳腺癌的T期呈正相关。此外，过表达的 miRNA-145-5p 还能显著抑制乳腺癌细胞的进展。生物信息分析预测 H2AFX 是 miRNA-145-5p 的潜在靶点，因此进行了双荧光素酶试验，结果表明 miRNA-145-5p 通过靶向 H2AFX 的 3'-UTR 负向调控其表达。拯救实验表明，过表达 miRNA-145-5p 可以抵消 oe-H2AFX 对恶性进展的促进作用：我们的研究旨在探索 miRNA-145-5p 在乳腺癌细胞中的功能：我们的研究结果证实，miRNA-145-5p通过负向调节H2AFX阻碍了乳腺癌的恶性进展。miRNA-145-5p/H2AFX轴可能是乳腺癌的一个新的治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Iranian Journal of Biotechnology BIOTECHNOLOGY & APPLIED MICROBIOLOGY-

CiteScore

2.60

自引率

7.70%

发文量

期刊介绍： Iranian Journal of Biotechnology (IJB) is published quarterly by the National Institute of Genetic Engineering and Biotechnology. IJB publishes original scientific research papers in the broad area of Biotechnology such as, Agriculture, Animal and Marine Sciences, Basic Sciences, Bioinformatics, Biosafety and Bioethics, Environment, Industry and Mining and Medical Sciences.