Shen Wenxiang, Liu Xiang, Wang Shengdong, Du Shaowen, Cong Liming, Ma Yulong, Ye Kaishan
Department of Orthopedics, Second Hospital of Lanzhou University, Lanzhou, China.
Key Laboratory of Bone and Joint Diseases of Gansu Province, Cui Ying Men 82 Hao, Lanzhou, 730000 Gansu Province China.
Cytotechnology. 2025 Jun;77(3):90. doi: 10.1007/s10616-025-00758-y. Epub 2025 Apr 21.
Osteosarcoma (OS), the most common primary malignant bone tumor in pediatric and adolescent populations, is characterized by significant morbidity and mortality. MicroRNAs (miRNAs) are essential non-coding RNAs that exert pivotal regulatory functions in diverse physiological and pathological processes, including tumorigenesis, disease progression, and drug resistance. The association of miR-34a-5p with osteosarcoma has been documented; However, its underlying mechanisms remain poorly understood.This investigation delineates the impact of miR-34a-5p on the proliferation, invasion, migration, and apoptosis of osteosarcoma cells via in vitro assays, aiming to elucidate the associated mechanisms. Employing up-regulation and knockdown strategies, this study evaluated the roles of miR-34a-5p and FoxM1 in modulating osteosarcoma cell behaviors.These effects were further validated through a rescue experiment, providing robust evidence of the miRNA's impact. Quantitative RT-PCR showed that, compared with normal tissues, miR-34a-5p was significantly downregulated while FoxM1 was markedly upregulated in nine osteosarcoma samples.Increased miR-34a-5p expression attenuated proliferation, migration, and invasion in MG-63 and U2OS cell lines, while enhancing apoptosis.Bioinformatic analyses and dual luciferase assays identified FoxM1 as a downstream target of miR-34a-5p, a finding corroborated by quantitative RT-PCR and Western blotting, which confirmed the negative regulation of FoxM1 by miR-34a-5p.Additionally, FoxM1 knockdown reduced tumor cell proliferation, migration, and invasion, concurrently promoting apoptosis; co-inhibition of miR-34a-5p and FoxM1 partially mitigated these effects. This study demonstrates that miR-34a-5p significantly inhibits osteosarcoma cell proliferation, migration, and invasion, while promoting apoptosis, by targeting and suppressing FoxM1. Our findings suggest that miR-34a-5p is a potential tumor suppressor with therapeutic value. The establishment of the miR-34a-5p/FoxM1 regulatory axis provides new insights into the molecular mechanisms of osteosarcoma. Targeting this axis could offer a promising strategy for improving the prognosis of osteosarcoma.
骨肉瘤（OS）是儿童和青少年人群中最常见的原发性恶性骨肿瘤，具有较高的发病率和死亡率。微小RNA（miRNA）是重要的非编码RNA，在包括肿瘤发生、疾病进展和耐药性在内的多种生理和病理过程中发挥关键调节作用。miR-34a-5p与骨肉瘤的关联已有文献记载；然而，其潜在机制仍知之甚少。本研究通过体外实验描述了miR-34a-5p对骨肉瘤细胞增殖、侵袭、迁移和凋亡的影响，旨在阐明相关机制。本研究采用上调和敲低策略，评估了miR-34a-5p和FoxM1在调节骨肉瘤细胞行为中的作用。通过挽救实验进一步验证了这些作用，为miRNA的影响提供了有力证据。定量逆转录聚合酶链反应（qRT-PCR）显示，与正常组织相比，在9例骨肉瘤样本中miR-34a-5p显著下调，而FoxM1明显上调。miR-34a-5p表达增加可减弱MG-63和U2OS细胞系的增殖、迁移和侵袭，同时增强细胞凋亡。生物信息学分析和双荧光素酶报告基因检测确定FoxM1是miR-34a-5p的下游靶点，qRT-PCR和蛋白质印迹法证实了这一发现，确证了miR-34a-5p对FoxM1的负调控作用。此外，敲低FoxM1可降低肿瘤细胞的增殖、迁移和侵袭，同时促进细胞凋亡；共同抑制miR-34a-5p和FoxM1可部分减轻这些作用。本研究表明，miR-34a-5p通过靶向并抑制FoxM1，显著抑制骨肉瘤细胞的增殖、迁移和侵袭，同时促进细胞凋亡。我们的研究结果表明，miR-34a-5p是一种具有治疗价值的潜在肿瘤抑制因子。miR-34a-5p/FoxM1调控轴的建立为骨肉瘤的分子机制提供了新的见解。靶向该轴可能为改善骨肉瘤的预后提供一种有前景的策略。
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