MALAT1 overexpression attenuates AS by inhibiting ox-LDL-stimulated dendritic cell maturation via miR-155-5p/NFIA axis

Li Chen; Liqun Hu; Xiang Zhu; Yan Wang; Qing Li; Jian Ma; Hongqi Li

doi:10.1080/15384101.2020.1807094

MALAT1 overexpression attenuates AS by inhibiting ox-LDL-stimulated dendritic cell maturation via miR-155-5p/NFIA axis

Cell Cycle. 2020 Oct;19(19):2472-2485. doi: 10.1080/15384101.2020.1807094. Epub 2020 Aug 25.

Authors

Li Chen¹, Liqun Hu¹, Xiang Zhu¹, Yan Wang¹, Qing Li², Jian Ma³, Hongqi Li¹

Affiliations

¹ Department of Gerontology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China; Anhui Provincial Hospital, Anhui Medical University , Hefei Anhui, 230001, P.R.China.
² The Central Laboratory of Medical Research Center, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China; Anhui Provincial Hospital, Anhui Medical University , Hefei Anhui, 230001, P.R.China.
³ Department of Cardiology, Department of Cardiology, Shanghai Sixth People's Hospital, Shanghai Jiaotong University , Shanghai, China.

Abstract

MALAT1 is associated with dendritic cells (DCs) maturation in Atherosclerosis (AS). This article aims to demystify the role of MALAT1 in AS. We separated immature DCs (iDCs) from healthy volunteers or ApoE-/- mice. And iDCs were treated with oxidized low density lipoprotein (ox-LDL) to induce DCs maturation. We found that ox-LDL promoted the levels of DCs maturation markers including CD83, CD86, IL-12 and IL-6. MALAT1 and NFIA were down-regulated, whereas miR-155-5p was up-regulated in the ox-LDL-treated iDCs. Furthermore, DCs maturation was notably suppressed by MALAT1 overexpression, NFIA overexpression or miR-155-5p knockdown. Moreover, MALAT1 functioned as a competing endogenous RNA to repress miR-155-5p, which controlled its down-stream target, NFIA. In addition, MALAT1 overexpression inhibited ox-LDL-stimulated DCs maturation by regulating miR-155-5p/NFIA axis. In AS mice, MALAT1 overexpression attenuated ox-LDL-stimulated DCs maturation and reduced atherosclerotic plaque area. In summary, our study demonstrates that MALAT1 overexpression attenuates AS by inhibiting ox-LDL-stimulated DCs maturation via miR-155-5p/NFIA axis. Thus, MALAT1/miR-155-5p/NFIA axis can potentially be used in the treatment of AS.

Keywords: MALAT1/miR-155-5p/NFIA; Ox-LDL; atherosclerosis; competing endogenous RNA; dendritic cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Atherosclerosis / genetics
Atherosclerosis / metabolism
Atherosclerosis / pathology
Atherosclerosis / prevention & control*
Dendritic Cells / drug effects*
Dendritic Cells / metabolism
Dendritic Cells / pathology
Disease Models, Animal
Humans
Lipoproteins, LDL / pharmacology*
Male
Mice, Knockout, ApoE
MicroRNAs / genetics
MicroRNAs / metabolism*
NFI Transcription Factors / genetics
NFI Transcription Factors / metabolism*
Plaque, Atherosclerotic
RNA, Long Noncoding / genetics
RNA, Long Noncoding / metabolism*
Signal Transduction
Up-Regulation

Substances

Lipoproteins, LDL
MALAT1 long non-coding RNA, human
MIRN155 microRNA, human
Malat1 long non-coding RNA, mouse
MicroRNAs
Mirn155 microRNA, mouse
NFI Transcription Factors
NFIA protein, human
Nfia protein, mouse
RNA, Long Noncoding
oxidized low density lipoprotein

Grants and funding

This project was supported by Natural Science Foundation of Anhui Province (1808085MH281); New Medicine of University of Science and Technology of China (WK9110000046); Anhui Provincial Cardiovascular Institute.