Bordbar Farhad, Rigi Amir, Mastanabad Mahsa Vafaei, Rohani Fattah, Ghaedi Elham, Dhiaa Shahad Mohammad, Asadi Fatemeh, Maragheh Salar Momen
Key Laboratory of Chicken Genetics, Breeding And Reproduction, Ministry of Agriculture And Rural Affair, South China Agricultural University, Guangzhou, Guangdong, 510642, China.
Department of Nursing, Young Researchers and Elite Club, Zahedan Branch, Islamic Azad University, Zahedan, Iran.
Cell Biochem Biophys. 2025 Jun;83(2):1605-1615. doi: 10.1007/s12013-024-01570-9. Epub 2024 Dec 12.
Neuroblastoma is a cancer that occurs due to abnormal development of the sympathetic nervous system. The dysregulation of miR-9 and miR-222 plays a crucial role in neuroblastoma development. These microRNAs have a significant relationship with PTEN, caspase-9, and MMP14, which can potentially form the basis for the specific diagnosis and treatment of this disease. In our study, two neuroblastoma cell lines were divided into three groups based on whether they had been treated with miR-9, anti-miR-9, miR-222, or both. We evaluated various parameters in these groups, including migration (through a wound healing assay), apoptosis (using flow cytometry), and gene expression (through qRT-PCR). Additionally, we measured the expression levels of MMP14, miR-9, and miR-222 in plasma and CSF samples from neuroblastoma patients using ELISA and qRT-PCR. We found that patients with neuroblastoma had higher levels of MMP14 and miR-222 mRNA expression but lower levels of miR-9 mRNA expression. Furthermore, after treating the cell lines with anti-miR-9 and anti-miR-222, we observed increased levels of MMP14 expression, as well as PTEN and caspase-9. Additionally, the treatment with anti-miR-222 and anti-miR-9 led to an increase in the frequency of apoptosis and migration of cancer cells. Our research shows that the dysregulation of miR-9, miR-222, and MMP14 could be key indicators in the pathogenesis of neuroblastoma. We also found that up-regulation of miR-9 was associated with decreased disease severity, whereas up-regulation of miR-222 and MMP14 was linked to increased disease severity.
神经母细胞瘤是一种由于交感神经系统异常发育而发生的癌症。miR-9和miR-222的失调在神经母细胞瘤的发展中起着关键作用。这些微小RNA与PTEN、半胱天冬酶-9和基质金属蛋白酶14有显著关系，这可能为该疾病的特异性诊断和治疗奠定基础。在我们的研究中，两种神经母细胞瘤细胞系根据是否用miR-9、抗miR-9、miR-222或两者进行处理被分为三组。我们评估了这些组中的各种参数，包括迁移（通过伤口愈合试验）、凋亡（使用流式细胞术）和基因表达（通过qRT-PCR）。此外，我们使用ELISA和qRT-PCR测量了神经母细胞瘤患者血浆和脑脊液样本中基质金属蛋白酶14、miR-9和miR-222的表达水平。我们发现神经母细胞瘤患者的基质金属蛋白酶14和miR-222 mRNA表达水平较高，但miR-9 mRNA表达水平较低。此外，在用抗miR-9和抗miR-222处理细胞系后，我们观察到基质金属蛋白酶14以及PTEN和半胱天冬酶-9的表达水平增加。此外，用抗miR-222和抗miR-9处理导致癌细胞凋亡和迁移频率增加。我们的研究表明，miR-9、miR-222和基质金属蛋白酶14的失调可能是神经母细胞瘤发病机制中的关键指标。我们还发现miR-9的上调与疾病严重程度降低相关，而miR-222和基质金属蛋白酶14的上调与疾病严重程度增加相关。
