Department of Integrated Biomedical Science, Soonchunhyang Institute of Medi-bio Science (SIMS), Soonchunhyang University, Chungcheongnam-do, Cheonan 31151, Korea.
Bundang CHA Medical Center, Department of Neurosurgery, CHA University, Yatap-dong 59, Seongnam 13496, Korea.
Genes (Basel). 2021 Apr 23;12(5):633. doi: 10.3390/genes12050633.
(1) Background: The elevation of glucose metabolism is linked to high-grade gliomas such as glioblastoma multiforme (GBM). The high glycolytic phenotype is associated with cellular proliferation and resistance to treatment with chemotherapeutic agents in GBM. MicroRNA-542-3p (miR-542-3p) has been implicated in several tumors including gliomas. However, the role of miR-542-3p in glucose metabolism in human gliomas remains unclear; (2) Methods: We measured the levels of cellular proliferation in human glioma cells. We measured the glycolytic activity in miR-542-3p knockdown and over-expressed human glioma cells. We measured the levels of miR-542-3p and HK2 in glioma tissues from patients with low- and high-grade gliomas using imaging analysis; (3) Results: We show that knockdown of miR-542-3p significantly suppressed cellular proliferation in human glioma cells. Knockdown of miR-542-3p suppressed HK2-induced glycolytic activity in human glioma cells. Consistently, over-expression of miR-542-3p increased HK2-induced glycolytic activity in human glioma cells. The levels of miR-542-3p and HK2 were significantly elevated in glioma tissues of patients with high-grade gliomas relative to that in low-grade gliomas. The elevation of HK2 levels in patients with high-grade gliomas were positively correlated with the high levels of miR-542-3p in GBM and low-grade gliomas (LGG) based on the datasets from the Cancer Genome Atlas (TCGA) database. Moreover, the high levels of miR-542-3p were associated with poor survival rate in the TCGA database; (4) Conclusions: miR-542-3p contributes to the HK2-mediated high glycolytic phenotype in human glioma cells.
（1）背景：葡萄糖代谢的升高与高级别神经胶质瘤（如多形性胶质母细胞瘤[GBM]）有关。在 GBM 中，高糖酵解表型与细胞增殖和对化疗药物治疗的抵抗有关。miR-542-3p（miR-542-3p）已被涉及多种肿瘤，包括神经胶质瘤。然而，miR-542-3p 在人类神经胶质瘤中的葡萄糖代谢中的作用尚不清楚；（2）方法：我们测量了人神经胶质瘤细胞的细胞增殖水平。我们测量了 miR-542-3p 敲低和过表达的人神经胶质瘤细胞的糖酵解活性。我们使用成像分析测量了来自低级别和高级别神经胶质瘤患者的神经胶质瘤组织中的 miR-542-3p 和 HK2 的水平；（3）结果：我们表明，miR-542-3p 的敲低显著抑制了人神经胶质瘤细胞的细胞增殖。miR-542-3p 的敲低抑制了 HK2 诱导的人神经胶质瘤细胞的糖酵解活性。一致地，miR-542-3p 的过表达增加了 HK2 诱导的人神经胶质瘤细胞的糖酵解活性。与低级别神经胶质瘤相比，高级别神经胶质瘤患者的神经胶质瘤组织中 miR-542-3p 和 HK2 的水平显著升高。基于癌症基因组图谱（TCGA）数据库中的数据集，高级别神经胶质瘤患者中 HK2 水平的升高与 GBM 和低级别神经胶质瘤（LGG）中 miR-542-3p 的高水平升高呈正相关。此外，在 TCGA 数据库中，miR-542-3p 的高水平与较差的生存率相关；（4）结论：miR-542-3p 有助于人神经胶质瘤细胞中 HK2 介导的高糖酵解表型。
