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  • LINC01198 facilitates gliomagenesis through activating PI3K/AKT pathway.

LINC01198 facilitates gliomagenesis through activating PI3K/AKT pathway.

RNA biology (2020-05-08)
Yuan Xie, Yuan Cheng
摘要

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.

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Triton X-100, laboratory grade
Sigma-Aldrich
Anti-RCOR1 antibody produced in rabbit, affinity isolated antibody