title: Quantitative Proteomics Analysis Reveals Novel Insights into Mechanisms of Action of Long Noncoding RNA Hox Transcript Antisense Intergenic RNA (HOTAIR) in HeLa Cells.
abstract: Long noncoding RNAs (lncRNAs), which have emerged in recent years as a new and crucial layer of gene regulators, regulate various biological processes such as carcinogenesis and metastasis. HOTAIR (Hox transcript antisense intergenic RNA), a lncRNA overexpressed in most human cancers, has been shown to be an oncogenic lncRNA. Here, we explored the role of HOTAIR in HeLa cells and searched for proteins regulated by HOTAIR. To understand the mechanism of action of HOTAIR from a systems perspective, we employed a quantitative proteomic strategy to systematically identify potential targets of HOTAIR. The expression of 170 proteins was significantly dys-regulated after inhibition of HOTAIR, implying that they could be potential targets of HOTAIR. Analysis of this data at the systems level revealed major changes in proteins involved in diverse cellular components, including the cytoskeleton and the respiratory chain. Further functional studies on vimentin (VIM), a key protein involved in the cytoskeleton, revealed that HOTAIR exerts its effects on migration and invasion of HeLa cells, at least in part, through the regulation of VIM expression. Inhibition of HOTAIR leads to mitochondrial dysfunction and ultrastructural alterations, suggesting a novel role of HOTAIR in maintaining mitochondrial function in cancer cells. Our results provide novel insights into the mechanisms underlying the function of HOTAIR in cancer cells. We expect that the methods used in this study will become an integral part of functional studies of lncRNAs.
authors.affiliation: From the ‡Key Laboratory of Algal Biology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China;
authors.forename: Peng
authors.initials: P
authors.lastname: Zheng
authors.affiliation: From the ‡Key Laboratory of Algal Biology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China;
authors.forename: Qian
authors.initials: Q
authors.lastname: Xiong
authors.affiliation: From the ‡Key Laboratory of Algal Biology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China;
authors.forename: Ying
authors.initials: Y
authors.lastname: Wu
authors.affiliation: From the ‡Key Laboratory of Algal Biology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China;
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: From the ‡Key Laboratory of Algal Biology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China;
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Chen
authors.affiliation: §Key Laboratory of Noncoding RNA, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China;
authors.forename: Joy
authors.initials: J
authors.lastname: Fleming
authors.affiliation: ¶State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
authors.forename: Ding
authors.initials: D
authors.lastname: Gao
authors.affiliation: §Key Laboratory of Noncoding RNA, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China;
authors.forename: Lijun
authors.initials: L
authors.lastname: Bi
authors.affiliation: From the ‡Key Laboratory of Algal Biology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China; gefeng@ihb.ac.cn.
authors.forename: Feng
authors.initials: F
authors.lastname: Ge
mesh_terms: D017209:Apoptosis; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005947:Glucose / Q000378:metabolism; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000502:physiology; D009369:Neoplasms / Q000378:metabolism; D060066:Protein Interaction Maps; D040901:Proteomics; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism; D014945:Wound Healing
chemical_list: C561566:HOTAIR long untranslated RNA, human; D062085:RNA, Long Noncoding; D017382:Reactive Oxygen Species; D014746:Vimentin; D005947:Glucose