MiR-371b-5p reduces osteosarcoma cell migration and proliferation to induce apoptosis by targeting FUT4.

IF 3.3 3区 医学 Q2 ONCOLOGY
Journal of Cancer Pub Date : 2025-04-13 eCollection Date: 2025-01-01 DOI:10.7150/jca.103286
Qiang Xue, Ruicong Ma, YueYuan Chen, Xiaodi Yan, Jiajia Liu, Jianhua Xue, Yang Yang, Xianchen Liu
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Abstract

In our previous study (PMID: 34671604), we found that miR-317b-5b not only exerted anti-tumor effect, but also downregulated FUT4 expression in human myeloma cell line 143B. This study aims to investigate the biological function of miR-371b-5p in osteosarcoma progression and the role of FUT4 in this process. For in vitro investigations, the human osteosarcoma cell lines (SaOS2, 143B, KHOS and U2OS) as well as the human osteoblast cell line (hFOB1.19) were employed as models. The QRT-PCR assay was utilized to determine the relative amounts of miR-371b-5p and FUT4 expression in the cells. The functions and effects of miR-371b-5p on the abilities to proliferate, migrate, apoptosis and invade of KHOS and U2OS in osteosarcoma cells were investigated using assays including CCK-8, colony formation, EDU, wound-healing, Western blot, TUNEL and Transwell assay. The correlations between miR-371b-5p, its downstream gene FUT4 and its potential mechanisms in mediating osteosarcoma progression were explored with the assistance of dual-luciferase reporter analysis together with rescue experiments. MiR-371b-5p was less expressed in osteosarcoma cells compared with osteoblasts. Its overexpression significantly inhibited the abilities to proliferate, invade and migrate to promote apoptosis of osteosarcoma cells. The correlations between FUT4 and miR-371b-5p was established by the gene analysis of the dual-luciferase reporter analysis. FUT4 expression was dramatically decreased after the process of miR-371b-5p mimics being transfected into KHOS and U2OS cells. Additionally, overexpression of FUT4 induced osteosarcoma cell apoptosis and partially overcame miR-371b-5p's inhibitory effects on osteosarcoma cell's abilities to proliferate, invade and migrate. Osteosarcoma cells exhibit down-regulation of miR-371b-5p, that prevents osteosarcoma cells from proliferating, invading and migrating in order to promote osteosarcoma cell apoptosis through concentrating on the breakdown of FUT4.

MiR-371b-5p通过靶向FUT4抑制骨肉瘤细胞迁移和增殖诱导细胞凋亡。
在我们之前的研究(PMID: 34671604)中,我们发现miR-317b-5b在人骨髓瘤细胞系143B中不仅具有抗肿瘤作用,还能下调FUT4的表达。本研究旨在探讨miR-371b-5p在骨肉瘤进展中的生物学功能以及FUT4在这一过程中的作用。体外实验以人骨肉瘤细胞系(SaOS2、143B、KHOS、U2OS)和人成骨细胞系(hFOB1.19)为模型。采用QRT-PCR检测细胞中miR-371b-5p和FUT4的相对表达量。采用CCK-8、集落形成、EDU、创面愈合、Western blot、TUNEL、Transwell等方法研究miR-371b-5p对骨肉瘤细胞KHOS、U2OS增殖、迁移、凋亡和侵袭能力的作用及影响。通过双荧光素酶报告基因分析和救援实验,探讨miR-371b-5p及其下游基因FUT4在骨肉瘤进展中的相关性及其潜在机制。与成骨细胞相比,MiR-371b-5p在骨肉瘤细胞中的表达较少。其过表达显著抑制骨肉瘤细胞的增殖、侵袭和迁移能力,促进骨肉瘤细胞凋亡。通过双荧光素酶报告基因分析,建立FUT4与miR-371b-5p之间的相关性。将miR-371b-5p模拟物转染到KHOS和U2OS细胞后,FUT4的表达显著降低。此外,过表达FUT4诱导骨肉瘤细胞凋亡,部分克服了miR-371b-5p对骨肉瘤细胞增殖、侵袭和迁移能力的抑制作用。骨肉瘤细胞下调miR-371b-5p,通过集中抑制FUT4的分解,阻止骨肉瘤细胞增殖、侵袭和迁移,从而促进骨肉瘤细胞凋亡。
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
Journal of Cancer
Journal of Cancer ONCOLOGY-
CiteScore
8.10
自引率
2.60%
发文量
333
审稿时长
12 weeks
期刊介绍: Journal of Cancer is an open access, peer-reviewed journal with broad scope covering all areas of cancer research, especially novel concepts, new methods, new regimens, new therapeutic agents, and alternative approaches for early detection and intervention of cancer. The Journal is supported by an international editorial board consisting of a distinguished team of cancer researchers. Journal of Cancer aims at rapid publication of high quality results in cancer research while maintaining rigorous peer-review process.
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