Dataset Information

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

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-1? mRNA and potentiate HIF-1? translation, leading to increased HIF-1? protein level, thereby promoting the Warburg effect and tumorigenesis. Importantly, PCED1B-AS1 lost the carcinogenic properties in the absence of HIF-1?. In addition, we also confirmed the existence of the PCED1B-AS1/HIF-1? regulatory axis in vivo. Taken together, our findings demonstrate that PCED1B-AS1 is a novel oncogenic lncRNA in GBM and functions in a HIF-1?-dependent manner, which provides a promising prognostic biomarker and druggable target for GBM.

SUBMITTER: Yao Z

PROVIDER: S-EPMC7444212 | biostudies-literature | 2020 Jan-Dec

REPOSITORIES: biostudies-literature

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Publications

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

Yao Zhiqiang Z Zhang Qiansheng Q Guo Fuyou F Guo Shewei S Yang Bo B Liu Binghui B Li Panxing P Li Jinyi J Guan Sheng S Liu Xianzhi X

Cell transplantation 20200101

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 signif ...[more]

PMID: 32326742

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Project description:OBJECTIVES:The long-noncoding RNAs (lncRNAs) are identified as new crucial regulators of diverse cellular processes in glioblastoma (GBM) tissues. However, the expression pattern and biological function of lncRNAs remain largely unknown. Here, for the first time, the effects of lncRNA lymphoid enhancer-binding factor 1 antisense RNA 1 (LEF1-AS1) on GBM progression both in vitro and in vivo are investigated. MATERIALS AND METHODS:Expression profiles of LEF1-AS1 in GBM specimens were investigated by bioinformatics analyses. LEF1-AS1 expression in GBM tissues was detected using a quantitative polymerase chain reaction. LEF1-AS1 expression was inhibited by transfecting the LEF1-AS1-specific small interfering RNAs (siRNAs) and stable cell lines established were inhibited by transfecting si-LEF1-AS1 viruses. The Cell Counting Kit-8, ethynyl deoxyuridine, and colony formation assay were used to examine proliferation function. The flow cytometry detected cell-cycle change and apoptosis. Migration effects were detected by a Transwell assay. The tumor xenografts and immunohistochemistry were performed to evaluate tumor growth in vivo. RESULTS:In this study, LEF1-AS1 expression was found significantly upregulated in GBM specimens compared with normal tissues. The 5-year overall survival in GBM patients from The Cancer Genome Atlas with high expression of LEF1-AS1 was inferior to that with low expression. It was confirmed that expression of LEF1-AS1 was higher in GBM tissues than normal ones. Knockdown of LEF1-AS1 significantly inhibited the malignancy of GBM cells, including proliferation and invasion, and promoted cell apoptosis. The result of Western blot assays indicated that knockdown of LEF1-AS1-mediated tumor suppression in GBM cells may be via the reduction of ERK and Akt/mTOR signaling activities. Finally, the in vivo experiment also demonstrated that knockdown LEF1-AS1 inhibited the growth-promoting effect of LEF1-AS1 of U87 cells. CONCLUSION:Our result indicated that lncRNA LEF1-AS1 acts as an oncogene in GBM and may be a pivotal target for this disease.

Dataset Information

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

Publications

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

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