Long Noncoding RNA PCED1B-AS1 Promotes the Warburg Effect and Tumorigenesis by Upregulating HIF-1α in Glioblastoma

长链非编码 RNA PCED1B-AS1 通过上调胶质母细胞瘤中的 HIF-1α 促进 Warburg 效应和肿瘤发生

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作者:Zhiqiang Yao, Qiansheng Zhang, Fuyou Guo, Shewei Guo, Bo Yang, Binghui Liu, Panxing Li, Jinyi Li, Sheng Guan, Xianzhi Liu

Abstract

Accumulating evidence suggests that long noncoding RNA (lncRNA) functions as a critical regulator in cancer biology. Here, we characterized the role of lncRNA PCED1B antisense RNA 1 (PCED1B-AS1) in glioblastoma (GBM). PCED1B-AS1 was notably upregulated in GBM tissues and cell lines and closely associated with larger tumor size and higher grade. Patients with high PCED1B-AS1 had shorter survival time than those with low PCED1B-AS1. Functional experiments showed that depletion of PCED1B-AS1 significantly inhibited, while overexpression of PCED1B-AS1 promoted cell proliferation, glucose uptake, and lactate release. Mechanistically, PCED1B-AS1 was able to directly bind to the 5'-UTR of HIF-1α mRNA and potentiate HIF-1α translation, leading to increased HIF-1α protein level, thereby promoting the Warburg effect and tumorigenesis. Importantly, PCED1B-AS1 lost the carcinogenic properties in the absence of HIF-1α. In addition, we also confirmed the existence of the PCED1B-AS1/HIF-1α regulatory axis in vivo. Taken together, our findings demonstrate that PCED1B-AS1 is a novel oncogenic lncRNA in GBM and functions in a HIF-1α-dependent manner, which provides a promising prognostic biomarker and druggable target for GBM.

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