Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, China.
NHC Key Laboratory of Carcinogenesis, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
Chin Med J (Engl). 2023 Jan 5;136(1):4-12. doi: 10.1097/CM9.0000000000002441.
Leucine-rich repeats containing 4 ( LRRC4 , also named netrin-G ligand 2 [NGL-2]) is a member of the NetrinGs ligands (NGLs) family. As a gene with relatively high and specific expression in brain, it is a member of the leucine-rich repeat superfamily and has been proven to be a suppressor gene for gliomas, thus being involved in gliomagenesis. LRRC4 is the core of microRNA-dependent multi-phase regulatory loops that inhibit the proliferation and invasion of glioblastoma (GB) cells, including LRRC4/NGL2-activator protein 2 (AP2)-microRNA (miR) 182-LRRC4 and LRRC4-miR185-DNA methyltransferase 1 (DNMT1)-LRRC4/specific protein 1 (SP1)-DNMT1-LRRC4. In this review, we demonstrated LRRC4 as a new member of the partitioning-defective protein (PAR) polarity complex that promotes axon differentiation, mediates the formation and plasticity of synapses, and assists information input to the hippocampus and storage of memory. As an important synapse regulator, aberrant expression of LRRC4 has been detected in autism, spinal injury and GBs. LRRC4 is a candidate susceptibility gene for autism and a neuro-protective factor in spinal nerve damage. In GBs, LRRC4 is a novel inhibitor of autophagy, and an inhibitor of protein-protein interactions involving in temozolomide resistance, tumor immune microenvironment, and formation of circular RNA.
富含亮氨酸重复序列 4（LRRC4，也称为神经导向因子 G 配体 2 [NGL-2]）是神经导向因子 Gs 配体（NGLs）家族的成员。作为一种在大脑中表达水平较高且具有特异性的基因，它是富含亮氨酸重复序列超家族的成员，已被证明是神经胶质瘤的抑制基因，从而参与神经胶质瘤的发生。LRRC4 是微 RNA 依赖性多相调控环路的核心，可抑制神经胶质瘤（GB）细胞的增殖和侵袭，包括 LRRC4/NGL2-激活蛋白 2（AP2）-微 RNA（miR）182-LRRC4 和 LRRC4-miR185-DNA 甲基转移酶 1（DNMT1）-LRRC4/特异性蛋白 1（SP1）-DNMT1-LRRC4。在本综述中，我们证明了 LRRC4 是一种新的有丝分裂缺陷蛋白（PAR）极性复合物的成员，它可促进轴突分化、介导突触的形成和可塑性，并协助海马体的信息输入和记忆存储。作为一种重要的突触调节因子，LRRC4 的异常表达已在自闭症、脊髓损伤和 GB 中被检测到。LRRC4 是自闭症的候选易感基因，也是脊髓神经损伤的神经保护因子。在 GB 中，LRRC4 是自噬的新型抑制剂，也是涉及替莫唑胺耐药、肿瘤免疫微环境和环状 RNA 形成的蛋白质-蛋白质相互作用的抑制剂。
