ErbB4-encoded novel miRNAs act as tumor suppressors by regulating ErbB/PI3K signaling.

Q3 Biochemistry, Genetics and Molecular Biology Tumor Biology Pub Date : 2022-01-01 DOI:10.3233/TUB-211570

Zahra Ghaemi, Bahram M Soltani, Seyed Javad Mowla

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引用次数: 3

Abstract

Background: ErbB/PI3K signaling is widely recognized as a critical modulator of malignancy and miRNAs have been found to play a crucial role in the regulation of this pathway.

Objective: This study aimed to identify novel miRNAs related to the ErbBs loci and investigate the functional effects of these miRNAs on ErbB/PI3K signaling in cancer progression.

Materials and methods: Bioinformatics tools and RNA-seq data were used to discover novel miRNAs in breast and colon cancer cells. Gene expression levels were determined using RT-qPCR. Western blotting and dual-luciferase assays were used to identify the regulatory mechanism between ErbB4-miR1/2 and related genes. The effects of ErbB4-miR1/2 on cell proliferation, viability, ROS production, and migration were assessed by PI-flow cytometry, colony formation, MTT, ROS, scratch, and transwell assays in SKBR3 and SW480 cells.

Results: MicroRNA prediction tools, RNA-seq data, RT-qPCR, and sequencing results identified ErbB4-miR1 and ErbB4-miR2 (ErbB4-miR1/2) as novel miRNAs encoded by ErbB4 gene. ErbB4-miR1/2 were downregulated in breast and colon tumor tissues and also in different cancerous cells. RT-qPCR and dual-luciferase assays revealed that ErbB2 and ErbB3 genes are regulated by ErbB4-miR1/2. Consistently, a decrease in the p-AKT/AKT protein ratio verified the suppressive effect of ErbB4-miR1/2 on ErbB/PI3K activity. Furthermore, ErbB4-miR1/2 overexpression suppressed cell proliferation, viability, and migration, and increased ROS production.

Conclusions: ErbB4-miR1/2 are novel tumor suppressor miRNAs which attenuate ErbB/PI3K signaling in breast and colon cancer cells.

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erbb4编码的新型mirna通过调节ErbB/PI3K信号传导而发挥肿瘤抑制作用。

背景:ErbB/PI3K信号被广泛认为是恶性肿瘤的关键调节剂，mirna在这一途径的调控中起着至关重要的作用。目的:本研究旨在鉴定与ErbB位点相关的新型mirna，并研究这些mirna在肿瘤进展中对ErbB/PI3K信号通路的功能影响。材料和方法:利用生物信息学工具和RNA-seq数据在乳腺癌和结肠癌细胞中发现新的mirna。采用RT-qPCR检测基因表达水平。采用Western blotting和双荧光素酶法鉴定ErbB4-miR1/2与相关基因之间的调控机制。在SKBR3和SW480细胞中，通过pi流式细胞术、集落形成、MTT、ROS、划痕和transwell检测来评估ErbB4-miR1/2对细胞增殖、活力、ROS产生和迁移的影响。结果:MicroRNA预测工具、RNA-seq数据、RT-qPCR和测序结果确定ErbB4- mir1和ErbB4- mir2 (ErbB4- mir1 /2)是ErbB4基因编码的新型mirna。ErbB4-miR1/2在乳腺和结肠肿瘤组织以及不同的癌细胞中表达下调。RT-qPCR和双荧光素酶检测显示ErbB2和ErbB3基因受ErbB4-miR1/2调控。同样，p-AKT/AKT蛋白比值的降低证实了ErbB4-miR1/2对ErbB/PI3K活性的抑制作用。此外，ErbB4-miR1/2过表达抑制细胞增殖、活力和迁移，并增加ROS的产生。结论:ErbB4-miR1/2是一种新型的肿瘤抑制mirna，可减弱乳腺癌和结肠癌细胞中的ErbB/PI3K信号。

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来源期刊

Tumor Biology 医学-肿瘤学

CiteScore

5.40

自引率

0.00%

发文量

审稿时长

1 months

期刊介绍： Tumor Biology is a peer reviewed, international journal providing an open access forum for experimental and clinical cancer research. Tumor Biology covers all aspects of tumor markers, molecular biomarkers, tumor targeting, and mechanisms of tumor development and progression. Specific topics of interest include, but are not limited to: Pathway analyses, Non-coding RNAs, Circulating tumor cells, Liquid biopsies, Exosomes, Epigenetics, Cancer stem cells, Tumor immunology and immunotherapy, Tumor microenvironment, Targeted therapies, Therapy resistance Cancer genetics, Cancer risk screening. Studies in other areas of basic, clinical and translational cancer research are also considered in order to promote connections and discoveries across different disciplines. The journal publishes original articles, reviews, commentaries and guidelines on tumor marker use. All submissions are subject to rigorous peer review and are selected on the basis of whether the research is sound and deserves publication. Tumor Biology is the Official Journal of the International Society of Oncology and BioMarkers (ISOBM).