LncRNA EPB41L4A-AS1 regulates glycolysis and glutaminolysis by mediating nucleolar translocation of HDAC2Research in context
Background: LncRNAs have been found to be involved in various aspects of biological processes. In this study, we aimed to uncover the molecular mechanisms of lncRNA EPB41L4A-AS1 in regulating glycolysis and glutaminolysis in cancer cells. Methods: The expression of EPB41L4A-AS1 in cancer patients wa...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2019-03-01
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| Series: | EBioMedicine |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396419300404 |
| _version_ | 1811205687232954368 |
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| author | Meijian Liao Weijie Liao Naihan Xu Bing Li Fuhai Liu Shikuan Zhang Yanzhi Wang Songmao Wang Yuanchang Zhu Deheng Chen Weidong Xie Yuyang Jiang Liu Cao Burton B. Yang Yaou Zhang |
| author_facet | Meijian Liao Weijie Liao Naihan Xu Bing Li Fuhai Liu Shikuan Zhang Yanzhi Wang Songmao Wang Yuanchang Zhu Deheng Chen Weidong Xie Yuyang Jiang Liu Cao Burton B. Yang Yaou Zhang |
| author_sort | Meijian Liao |
| collection | DOAJ |
| description | Background: LncRNAs have been found to be involved in various aspects of biological processes. In this study, we aimed to uncover the molecular mechanisms of lncRNA EPB41L4A-AS1 in regulating glycolysis and glutaminolysis in cancer cells. Methods: The expression of EPB41L4A-AS1 in cancer patients was analyzed in TCGA and GEO datasets. The level of cellular metabolism was determined by extracellular flux analyzer. The relationship between p53 and EPB41L4A-AS1 was explored by qRT-PCR, luciferase assay and ChIP assay. The interactions between EPB41L4A-AS1 and HDAC2 or NPM1 were determined by RNA immunoprecipitation, RNA pull-down assay and RNA-FISH- immunofluorescence. Findings: EPB41L4A-AS1 was a p53-regulated gene. Low expression and deletion of lncRNA EPB41L4A-AS1 were found in a variety of human cancers and associated with poor prognosis of cancer patients. Knock down EPB41L4A-AS1 expression triggered Warburg effect, demonstrated as increased aerobic glycolysis and glutaminolysis. EPB41L4A-AS1 interacted and colocalized with HDAC2 and NPM1 in nucleolus. Silencing EPB41L4A-AS1 reduced the interaction between HDAC2 and NPM1, released HDAC2 from nucleolus and increased its distribution in nucleoplasm, enhanced HDAC2 occupation on VHL and VDAC1 promoter regions, and finally accelerated glycolysis and glutaminolysis. Depletion of EPB41L4A-AS1 increased the sensitivity of tumor to glutaminase inhibitor in tumor therapy. Interpretation: EPB41L4A-AS1 functions as a repressor of the Warburg effect and plays important roles in metabolic reprogramming of cancer. Keywords: EPB41L4A-AS1, HDAC2, Glycolysis, Glutaminolysis, Cancer metabolism |
| first_indexed | 2024-04-12T03:35:14Z |
| format | Article |
| id | doaj.art-242c4ddbbe5b474e800485c46f545c58 |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-04-12T03:35:14Z |
| publishDate | 2019-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-242c4ddbbe5b474e800485c46f545c582022-12-22T03:49:26ZengElsevierEBioMedicine2352-39642019-03-0141200213LncRNA EPB41L4A-AS1 regulates glycolysis and glutaminolysis by mediating nucleolar translocation of HDAC2Research in contextMeijian Liao0Weijie Liao1Naihan Xu2Bing Li3Fuhai Liu4Shikuan Zhang5Yanzhi Wang6Songmao Wang7Yuanchang Zhu8Deheng Chen9Weidong Xie10Yuyang Jiang11Liu Cao12Burton B. Yang13Yaou Zhang14School of Life Sciences, Tsinghua University, Beijing 100084, PR China; Key Lab in Healthy Science and Technology, Division of Life Science, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, PR ChinaSchool of Life Sciences, Tsinghua University, Beijing 100084, PR China; Key Lab in Healthy Science and Technology, Division of Life Science, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, PR ChinaState Key Laboratory of Chemical Oncogenomics, Graduate School at Shenzhen, Tsinghua University, Shenzhen, PR China; Key Lab in Healthy Science and Technology, Division of Life Science, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, PR China; Open FIESTA Center, Tsinghua University, Shenzhen 518055, PR ChinaSchool of Life Sciences, Tsinghua University, Beijing 100084, PR China; Key Lab in Healthy Science and Technology, Division of Life Science, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, PR ChinaKey Lab in Healthy Science and Technology, Division of Life Science, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, PR China; Open FIESTA Center, Tsinghua University, Shenzhen 518055, PR ChinaSchool of Life Sciences, Tsinghua University, Beijing 100084, PR China; Key Lab in Healthy Science and Technology, Division of Life Science, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, PR ChinaSchool of Life Sciences, Tsinghua University, Beijing 100084, PR China; Key Lab in Healthy Science and Technology, Division of Life Science, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, PR ChinaKey Lab in Healthy Science and Technology, Division of Life Science, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, PR ChinaSchool of Life Sciences, Tsinghua University, Beijing 100084, PR China; Key Lab in Healthy Science and Technology, Division of Life Science, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, PR ChinaSecond Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen 518055, PR ChinaState Key Laboratory of Chemical Oncogenomics, Graduate School at Shenzhen, Tsinghua University, Shenzhen, PR China; Key Lab in Healthy Science and Technology, Division of Life Science, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, PR China; Open FIESTA Center, Tsinghua University, Shenzhen 518055, PR ChinaState Key Laboratory of Chemical Oncogenomics, Graduate School at Shenzhen, Tsinghua University, Shenzhen, PR ChinaKey Laboratory of Medical Cell Biology, China Medical University, Shenyang 110013, PR China; Corresponding authors.Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Corresponding authors.State Key Laboratory of Chemical Oncogenomics, Graduate School at Shenzhen, Tsinghua University, Shenzhen, PR China; Key Lab in Healthy Science and Technology, Division of Life Science, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, PR China; Open FIESTA Center, Tsinghua University, Shenzhen 518055, PR China; Corresponding author at: State Key Laboratory of Chemical Oncogenomics, Graduate School at Shenzhen, Tsinghua University, Shenzhen, PR ChinaBackground: LncRNAs have been found to be involved in various aspects of biological processes. In this study, we aimed to uncover the molecular mechanisms of lncRNA EPB41L4A-AS1 in regulating glycolysis and glutaminolysis in cancer cells. Methods: The expression of EPB41L4A-AS1 in cancer patients was analyzed in TCGA and GEO datasets. The level of cellular metabolism was determined by extracellular flux analyzer. The relationship between p53 and EPB41L4A-AS1 was explored by qRT-PCR, luciferase assay and ChIP assay. The interactions between EPB41L4A-AS1 and HDAC2 or NPM1 were determined by RNA immunoprecipitation, RNA pull-down assay and RNA-FISH- immunofluorescence. Findings: EPB41L4A-AS1 was a p53-regulated gene. Low expression and deletion of lncRNA EPB41L4A-AS1 were found in a variety of human cancers and associated with poor prognosis of cancer patients. Knock down EPB41L4A-AS1 expression triggered Warburg effect, demonstrated as increased aerobic glycolysis and glutaminolysis. EPB41L4A-AS1 interacted and colocalized with HDAC2 and NPM1 in nucleolus. Silencing EPB41L4A-AS1 reduced the interaction between HDAC2 and NPM1, released HDAC2 from nucleolus and increased its distribution in nucleoplasm, enhanced HDAC2 occupation on VHL and VDAC1 promoter regions, and finally accelerated glycolysis and glutaminolysis. Depletion of EPB41L4A-AS1 increased the sensitivity of tumor to glutaminase inhibitor in tumor therapy. Interpretation: EPB41L4A-AS1 functions as a repressor of the Warburg effect and plays important roles in metabolic reprogramming of cancer. Keywords: EPB41L4A-AS1, HDAC2, Glycolysis, Glutaminolysis, Cancer metabolismhttp://www.sciencedirect.com/science/article/pii/S2352396419300404 |
| spellingShingle | Meijian Liao Weijie Liao Naihan Xu Bing Li Fuhai Liu Shikuan Zhang Yanzhi Wang Songmao Wang Yuanchang Zhu Deheng Chen Weidong Xie Yuyang Jiang Liu Cao Burton B. Yang Yaou Zhang LncRNA EPB41L4A-AS1 regulates glycolysis and glutaminolysis by mediating nucleolar translocation of HDAC2Research in context EBioMedicine |
| title | LncRNA EPB41L4A-AS1 regulates glycolysis and glutaminolysis by mediating nucleolar translocation of HDAC2Research in context |
| title_full | LncRNA EPB41L4A-AS1 regulates glycolysis and glutaminolysis by mediating nucleolar translocation of HDAC2Research in context |
| title_fullStr | LncRNA EPB41L4A-AS1 regulates glycolysis and glutaminolysis by mediating nucleolar translocation of HDAC2Research in context |
| title_full_unstemmed | LncRNA EPB41L4A-AS1 regulates glycolysis and glutaminolysis by mediating nucleolar translocation of HDAC2Research in context |
| title_short | LncRNA EPB41L4A-AS1 regulates glycolysis and glutaminolysis by mediating nucleolar translocation of HDAC2Research in context |
| title_sort | lncrna epb41l4a as1 regulates glycolysis and glutaminolysis by mediating nucleolar translocation of hdac2research in context |
| url | http://www.sciencedirect.com/science/article/pii/S2352396419300404 |
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