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

• Published in: Cell transplantation Vol. 29; p. 96368972090677
• Main Authors: Yao, Zhiqiang, Zhang, Qiansheng, Guo, Fuyou, Guo, Shewei, Yang, Bo, Liu, Binghui, Li, Panxing, Li, Jinyi, Guan, Sheng, Liu, Xianzhi
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 01.01.2020; Sage Publications Ltd; SAGE Publishing
• Subjects: 5' Untranslated Regions; Antisense RNA; Antisense therapy; Brain cancer; Cell Line, Tumor; Cell proliferation; Female; Gene Expression Regulation, Neoplastic - genetics; Gene Expression Regulation, Neoplastic - physiology; Glioblastoma; Glioblastoma - genetics; Glioblastoma - pathology; Humans; Hypoxia-Inducible Factor 1, alpha Subunit - genetics; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Hypoxia-inducible factor 1a; Lactic acid; Male; Middle Aged; mRNA; Original; RNA, Long Noncoding - genetics; Tumorigenesis; Warburg Effect, Oncologic; long noncoding RNA; translation; tumorigenesis; biomarker; Warburg effect
• ISSN: 0963-6897; 1555-3892; 1555-3892
• DOI: 10.1177/0963689720906777

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.