Glioma is the most malignant primary brain cancer which frequently occurred in adults. In recent years, long-non coding RNAs (lncRNAs) have been demonstrated to play pivotal roles in human cancers. However, the role of most lncRNAs in gliomagenesis has not been probed. Presently, through TCGA, a novel lncRNA LINC01198 was found to be up-regulated and associated with clinical outcomes in glioblastoma multiforme (GBM). In our study, LINC01198 was proved to be up-regulated in glioma cell lines, and silenced LINC01198 curbed glioma cell proliferation and accelerated cell apoptosis. Importantly, we corroborated that LINC01198 activated the PI3 K/AKT pathway to aggravate glioma progression by targeting PIK3 CA and PTEN. Subsequently, LINC01198 was validated to localize in both cytoplasm and nucleus of glioma cells. Through mechanistic exploration, we illustrated that LINC01198 increased PIK3CA expression by sponging miR-129-5p in the cytoplasm. Furthermore, PTEN was transcriptionally repressed by REST/RCOR1/HDAC2 complex. More importantly, LINC01198 accelerated the assembly of REST/RCOR1/HDAC2 complex and recruited such complex to PTEN promoter so as to impair PTEN expression in glioma. Finally, we further verified that LINC01198 hindered glioma tumour growth in vivo through AKT-dependent manner. Jointly, LINC01198 activates PI3 K/AKT signalling to exert oncogenic function in gliomagenesis by regulating PIK3CA and PTEN, which highlights a new approach for glioma treatment.

胶质瘤是最恶性的原发性脑癌，经常在成人中发生。近年来，已证明长非编码RNA（lncRNA）在人类癌症中起关键作用。但是，大多数lncRNA在神经胶质瘤发生中的作用尚未探明。目前，通过TCGA，发现一种新型的lncRNA LINC01198在多形性胶质母细胞瘤（GBM）中被上调并与临床结果相关。在我们的研究中，LINC01198被证明在神经胶质瘤细胞系中被上调，而沉默的LINC01198则抑制了神经胶质瘤细胞的增殖并加速了细胞凋亡。重要的是，我们证实了LINC01198通过靶向PIK3 CA和PTEN激活了PI3 K / AKT通路，从而加剧了神经胶质瘤的进展。随后，LINC01198被验证可以定位在神经胶质瘤细胞的细胞质和细胞核中。通过机械探索，我们阐明了LINC01198通过在细胞质中海绵化miR-129-5p来增加PIK3CA表达。此外，PTEN被REST / RCOR1 / HDAC2复合体转录抑制。更重要的是，LINC01198加速了REST / RCOR1 / HDAC2复合物的组装，并将这种复合物募集到PTEN启动子，从而损害了神经胶质瘤中PTEN的表达。最后，我们进一步证实LINC01198通过AKT依赖性方式在体内阻碍神经胶质瘤的生长。LINC01198联合激活PI3 K / AKT信号传导，通过调节PIK3CA和PTEN在神经胶质瘤的发生中发挥致癌作用，这突显了神经胶质瘤治疗的新方法。LINC01198加速了REST / RCOR1 / HDAC2复合物的组装，并将这种复合物募集到PTEN启动子，从而损害了神经胶质瘤中PTEN的表达。最后，我们进一步证实LINC01198通过AKT依赖性方式在体内阻碍神经胶质瘤的生长。LINC01198联合激活PI3 K / AKT信号传导，通过调节PIK3CA和PTEN在神经胶质瘤的发生中发挥致癌作用，这突显了神经胶质瘤治疗的新方法。LINC01198加速了REST / RCOR1 / HDAC2复合物的组装，并将这种复合物募集到PTEN启动子，从而损害了神经胶质瘤中PTEN的表达。最后，我们进一步证实LINC01198通过AKT依赖性方式在体内阻碍了神经胶质瘤的生长。LINC01198联合激活PI3 K / AKT信号传导，通过调节PIK3CA和PTEN在神经胶质瘤的发生中发挥致癌作用，这突显了神经胶质瘤治疗的新方法。