Long Noncoding RNA PCED1B-AS1 Promotes the Warburg Effect and Tumorigenesis by Upregulating HIF-1α in Glioblastoma
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 assoc...
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| Published in | Cell transplantation Vol. 29; p. 96368972090677 |
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| Main Authors | , , , , , , , , , |
| Format | Journal Article |
| Language | English |
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SAGE Publications
01.01.2020
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| 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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| AbstractList | 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. 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.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. 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. |
| Author | Guo, Shewei Li, Jinyi Zhang, Qiansheng Guan, Sheng Yang, Bo Liu, Binghui Guo, Fuyou Li, Panxing Yao, Zhiqiang Liu, Xianzhi |
| AuthorAffiliation | 1 Department of Interventional Neuroradiology, The First Affiliated Hospital of Zhengzhou University, Henan, China 3 Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Henan, China 2 Department of Neurosurgery, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, Henan, China |
| AuthorAffiliation_xml | – name: 1 Department of Interventional Neuroradiology, The First Affiliated Hospital of Zhengzhou University, Henan, China – name: 3 Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Henan, China – name: 2 Department of Neurosurgery, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, Henan, China |
| Author_xml | – sequence: 1 givenname: Zhiqiang surname: Yao fullname: Yao, Zhiqiang – sequence: 2 givenname: Qiansheng surname: Zhang fullname: Zhang, Qiansheng – sequence: 3 givenname: Fuyou surname: Guo fullname: Guo, Fuyou – sequence: 4 givenname: Shewei surname: Guo fullname: Guo, Shewei – sequence: 5 givenname: Bo surname: Yang fullname: Yang, Bo – sequence: 6 givenname: Binghui surname: Liu fullname: Liu, Binghui email: liuxz85@yeah.net – sequence: 7 givenname: Panxing surname: Li fullname: Li, Panxing email: liuxz85@yeah.net – sequence: 8 givenname: Jinyi surname: Li fullname: Li, Jinyi email: liuxz85@yeah.net – sequence: 9 givenname: Sheng surname: Guan fullname: Guan, Sheng email: guanszz6@126.com – sequence: 10 givenname: Xianzhi orcidid: 0000-0003-3965-1815 surname: Liu fullname: Liu, Xianzhi email: liuxz85@yeah.net |
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| Keywords | long noncoding RNA translation tumorigenesis biomarker Warburg effect |
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| Snippet | Accumulating evidence suggests that long noncoding RNA (lncRNA) functions as a critical regulator in cancer biology. Here, we characterized the role of lncRNA... Accumulating evidence suggests that long noncoding RNA (lncRNA) functions as a critical regulator in cancer biology. Here, we characterized the role of lncRNA... |
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| SubjectTerms | 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 |
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| Title | Long Noncoding RNA PCED1B-AS1 Promotes the Warburg Effect and Tumorigenesis by Upregulating HIF-1α in Glioblastoma |
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