Cellular Signalling Laboratory, Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Bologna, Italy.
Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy; Pituitary Unit, IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy.
Adv Biol Regul. 2022 Jan;83:100838. doi: 10.1016/j.jbior.2021.100838. Epub 2021 Nov 19.
Phosphoinositide-specific phospholipases C (PLCs) are a class of enzymes involved in several cell activities, such as cell cycle regulation, proliferation, differentiation and cytoskeletal dynamics. Among these enzymes, PLCγ1 is one of the most expressed PLCs in the brain, contributing to a complex network in the developing nervous system. Several studies have shown that PLCγ1 signaling imbalance is linked to several brain disorders, including glioblastoma, the most aggressive brain tumor in adults. Indeed, it has been demonstrated a link between PLCγ1 inhibition and the arrest of glioma cell motility of fetal rat brain aggregates and the impairment of cell invasion abilities following its down-regulation. This study aims to determine the pathological influence of PLCγ1 in glioblastoma, through a translational study which combines in silico data, data from glioblastoma patients' samples and data on engineered cell lines. We found out that PLCγ1 gene expression correlates with the pathological grade of gliomas, and it is higher in fifty patients' glioblastoma tissue samples compared to twenty healthy controls. Moreover, it was demonstrated that PLCγ1 silencing in U87-MG leads to a reduction in cell migration and invasion abilities. The opposite trend was observed following PLCγ1 overexpression, suggesting an interesting possible involvement of PLCγ1 in gliomas' aggressiveness.
磷酸肌醇特异性磷脂酶 C（PLCs）是一类参与多种细胞活动的酶，如细胞周期调节、增殖、分化和细胞骨架动力学。在这些酶中，PLCγ1 是大脑中表达最丰富的 PLC 之一，在发育中的神经系统中形成一个复杂的网络。几项研究表明，PLCγ1 信号失衡与几种脑部疾病有关，包括胶质母细胞瘤，这是成人中最具侵袭性的脑肿瘤。事实上，已经证明 PLCγ1 抑制与胎鼠脑聚集物中神经胶质瘤细胞运动的阻滞以及其下调后细胞侵袭能力的损害之间存在联系。这项研究旨在通过一项结合了计算机数据、胶质母细胞瘤患者样本数据和工程细胞系数据的转化研究，确定 PLCγ1 在胶质母细胞瘤中的病理影响。我们发现 PLCγ1 基因表达与胶质瘤的病理分级相关，在 50 名患者的胶质母细胞瘤组织样本中高于 20 名健康对照者。此外，证明在 U87-MG 中沉默 PLCγ1 会导致细胞迁移和侵袭能力的降低。相反，过表达 PLCγ1 则观察到相反的趋势，表明 PLCγ1 可能在神经胶质瘤的侵袭性中具有有趣的潜在作用。
