Guo Zeshang, An Pingxv, Hong Xinyu
Department of Neurosurgery, The First Hospital of Jilin University, Changchun, Jilin 130021, China.
Aging (Albany NY). 2024 Apr 4;16(7):6510-6520. doi: 10.18632/aging.205720.
Our research investigated the effects of hsa-miR-134-5p on glioma progression, focusing on its interaction with the BDNF/ERK signaling pathway. U251 and U87 cell lines were analyzed post-transfection with hsa-miR-134-5p mimics and inhibitors, confirming the miRNA's binding to BDNF using dual luciferase assays. Q-PCR was employed to measure expression changes, revealing that hsa-miR-134-5p markedly inhibited glioma cell proliferation, migration, and invasion, as evidenced by CCK8, monoclonal formation, and Transwell assays. Scratch tests and Western blotting demonstrated hsa-miR-134-5p's modulation of the BDNF/ERK pathway and associated decrease in MMP2/9 protein levels. Flow cytometry suggested that hsa-miR-134-5p might also block the G0/S phase transition. studies using nude mice corroborated the tumor-suppressing effects of hsa-miR-134-5p, which were negated by elevated BDNF levels. Comparative protein analysis across groups confirmed the pathway's significance in tumorigenesis. Our findings identify hsa-miR-134-5p as a key molecule impeding glioma cell growth by curtailing the BDNF/ERK pathway, with the reversal by BDNF upregulation pointing to the potential of therapeutically exploiting the hsa-miR-134-5p/BDNF axis in glioma care.
我们的研究调查了hsa-miR-134-5p对胶质瘤进展的影响，重点关注其与BDNF/ERK信号通路的相互作用。在用hsa-miR-134-5p模拟物和抑制剂转染后，对U251和U87细胞系进行了分析，并使用双荧光素酶测定法确认了该miRNA与BDNF的结合。采用Q-PCR测量表达变化，结果显示hsa-miR-134-5p显著抑制胶质瘤细胞的增殖、迁移和侵袭，CCK8、单克隆形成和Transwell测定法均证实了这一点。划痕试验和蛋白质印迹法表明hsa-miR-134-5p对BDNF/ERK通路具有调节作用，并导致MMP2/9蛋白水平相应降低。流式细胞术表明hsa-miR-134-5p可能还会阻断G0/S期转换。使用裸鼠进行的研究证实了hsa-miR-134-5p的肿瘤抑制作用，而BDNF水平升高则会抵消这种作用。各实验组之间的蛋白质对比分析证实了该通路在肿瘤发生中的重要性。我们的研究结果表明，hsa-miR-134-5p是通过抑制BDNF/ERK通路来阻碍胶质瘤细胞生长的关键分子，BDNF上调导致的作用逆转表明在胶质瘤治疗中利用hsa-miR-134-5p/BDNF轴具有潜在的治疗价值。
