Overexpression of lncRNA EPB41L4A-AS1 Induces Metabolic Reprogramming in Trophoblast Cells and Placenta Tissue of Miscarriage

Yuanchang Zhu; Qing Liu; Meijian Liao; Lianghui Diao; Tonghua Wu; Weijie Liao; Ziqiang Wang; Bing Li; Shikuan Zhang; Songmao Wang; Weidong Xie; Yuyang Jiang; Naihan Xu; Yong Zeng; Burton B. Yang; Yaou Zhang

Molecular Therapy: Nucleic Acids (Dec 2019)

Overexpression of lncRNA EPB41L4A-AS1 Induces Metabolic Reprogramming in Trophoblast Cells and Placenta Tissue of Miscarriage

Yuanchang Zhu,
Qing Liu,
Meijian Liao,
Lianghui Diao,
Tonghua Wu,
Weijie Liao,
Ziqiang Wang,
Bing Li,
Shikuan Zhang,
Songmao Wang,
Weidong Xie,
Yuyang Jiang,
Naihan Xu,
Yong Zeng,
Burton B. Yang,
Yaou Zhang

Affiliations

Yuanchang Zhu: School of Life Sciences, Tsinghua University, Beijing 100084, P.R. China; Key Lab in Healthy Science and Technology, Division of Life Science, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, P.R. China; State Key Laboratory of Chemical Oncogenomics, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, P.R. China
Qing Liu: School of Life Sciences, Tsinghua University, Beijing 100084, P.R. China; Key Lab in Healthy Science and Technology, Division of Life Science, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, P.R. China; State Key Laboratory of Chemical Oncogenomics, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, P.R. China
Meijian Liao: School of Life Sciences, Tsinghua University, Beijing 100084, P.R. China; Key Lab in Healthy Science and Technology, Division of Life Science, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, P.R. China; State Key Laboratory of Chemical Oncogenomics, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, P.R. China
Lianghui Diao: Shenzhen Key Laboratory for Reproductive Immunology of Preimplantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen 518055, P.R. China
Tonghua Wu: Shenzhen Key Laboratory for Reproductive Immunology of Preimplantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen 518055, P.R. China
Weijie Liao: School of Life Sciences, Tsinghua University, Beijing 100084, P.R. China; Key Lab in Healthy Science and Technology, Division of Life Science, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, P.R. China
Ziqiang Wang: School of Life Sciences, Tsinghua University, Beijing 100084, P.R. China; Key Lab in Healthy Science and Technology, Division of Life Science, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, P.R. China
Bing Li: School of Life Sciences, Tsinghua University, Beijing 100084, P.R. China; Key Lab in Healthy Science and Technology, Division of Life Science, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, P.R. China
Shikuan Zhang: School of Life Sciences, Tsinghua University, Beijing 100084, P.R. China; State Key Laboratory of Chemical Oncogenomics, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, P.R. China
Songmao Wang: School of Life Sciences, Tsinghua University, Beijing 100084, P.R. China; Key Lab in Healthy Science and Technology, Division of Life Science, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, P.R. China
Weidong Xie: Key Lab in Healthy Science and Technology, Division of Life Science, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, P.R. China; State Key Laboratory of Chemical Oncogenomics, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, P.R. China; Open FIESTA Center, Tsinghua University, Shenzhen 518055, P.R. China
Yuyang Jiang: Key Lab in Healthy Science and Technology, Division of Life Science, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, P.R. China
Naihan Xu: Key Lab in Healthy Science and Technology, Division of Life Science, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, P.R. China; State Key Laboratory of Chemical Oncogenomics, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, P.R. China; Open FIESTA Center, Tsinghua University, Shenzhen 518055, P.R. China
Yong Zeng: Shenzhen Key Laboratory for Reproductive Immunology of Preimplantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen 518055, P.R. China
Burton B. Yang: Sunnybrook Research Institute and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; Corresponding author: Burton B. Yang, Sunnybrook Research Institute and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
Yaou Zhang: Key Lab in Healthy Science and Technology, Division of Life Science, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, P.R. China; State Key Laboratory of Chemical Oncogenomics, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, P.R. China; Open FIESTA Center, Tsinghua University, Shenzhen 518055, P.R. China; Corresponding author: Yaou Zhang, Key Lab in Healthy Science and Technology, Division of Life Science, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, P.R. China.

Journal volume & issue: Vol. 18
pp. 518 – 532

Abstract

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Long non-coding RNAs (lncRNAs) have been shown to be crucial regulators in numerous human diseases. However, little is known about their effects on early recurrent miscarriage (RM). Here we aimed to investigate the role of lncRNA EPB41L4A-AS1 on placental trophoblast cell metabolic reprogramming, which might be involved in the pathogenesis of RM. After microarray and GEO database analyses, we found that EPB41L4A-AS1 was significantly increased in early RM placental tissue, and this increase may relate to estradiol-mediated upregulation of PGC-1α. EPB41L4A-AS1 overexpression inhibits glycolysis but increases the dependence on fatty acid oxidation in mitochondrion metabolism and suppresses the Warburg effect, which is necessary for rapid growth of the placental villus, leading to miscarriage. Mechanistic analyses demonstrated that EPB41L4A-AS1 functions as a lncRNA in the regulation of VDAC1 and HIF-1α expression through enhancement of H3K4me3 levels in the promoters of VDAC1 and HIF1A-AS1, a natural antisense transcript (NAT) lncRNA of HIF-1α. Taken together, these findings demonstrate that aberrant expression of EPB41L4A-AS1 is involved in the etiology of early RM, and it may be a candidate diagnostic hallmark and a potential therapeutic target for early RM treatment. Keywords: lncRNA EPB41L4A-AS1, HIF-1α, VDAC1, recurrent miscarriage, metabolic reprogramming

Published in Molecular Therapy: Nucleic Acids

ISSN: 2162-2531 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.cell.com/molecular-therapy-family/nucleic-acids/latest-content

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