Open Access

Long non‑coding RNA MALAT1 regulates cholesterol accumulation in ox‑LDL‑induced macrophages via the microRNA‑17‑5p/ABCA1 axis

  • Authors:
    • Limin Liu
    • Lili Tan
    • Jian Yao
    • Lin Yang
  • View Affiliations

  • Published online on: February 13, 2020     https://doi.org/10.3892/mmr.2020.10987
  • Pages: 1761-1770
  • Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Atherosclerosis (AS), a major cause of cardiovascular disease, has developed into a serious challenge to the health system. The long non‑coding RNA (lncRNA) metastasis associated lung adenocarcinoma transcript 1 (MALAT1) is associated with the pathogenesis of AS. However, whether MALAT1 can affect cholesterol accumulation in macrophages during AS progression, and the potential molecular mechanism involved in this progression have not been elucidated. In the present study, the mRNA expression level of MALAT1 was measured using reverse transcription‑quantitative PCR (RT‑qPCR) and the protein expression level was detected via western blot analysis. Oil Red O staining was used for detecting lipid accumulation in macrophages. Bioinformatics, dual‑luciferase reporter and RT‑qPCR assays were used to investigate the relationship between MALAT1 and the microRNA (miR)‑17‑5p/ATP‑binding cassette transporter A1 (ABCA1) axis. The present results suggested that the MALAT1 expression level was significantly decreased in patients with AS and in oxidized low‑density lipoprotein (ox‑LDL)‑stimulated macrophages. Knockdown of MALAT1 increased ox‑LDL uptake, lipid accumulation and the total cholesterol (T‑CHO) level in ox‑LDL‑induced macrophages. In addition, MALAT1 inhibition significantly decreased the mRNA and protein expression levels of scavenger receptor (SR) class B member 1, apolipoprotein E (ApoE) and ABCA1. However, MALAT1 increased the expression level of SR class A. Subsequently, the present study investigated whether MALAT1 could target miR‑17‑5p to regulate the expression level of ABCA1, which is involved in cholesterol efflux from macrophages. The present results suggested that inhibition of miR‑17‑5p reversed the effects of MALAT1 knockdown on T‑CHO content, and protein expression levels of ApoE and ABCA1 in ox‑LDL‑stimulated macrophages. In summary, knockdown of MALAT1 may promote cholesterol accumulation by regulating the miR‑17‑5p/ABCA1 axis in ox‑LDL‑induced THP‑1 macrophages.
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April-2020
Volume 21 Issue 4

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Liu L, Tan L, Yao J and Yang L: Long non‑coding RNA MALAT1 regulates cholesterol accumulation in ox‑LDL‑induced macrophages via the microRNA‑17‑5p/ABCA1 axis. Mol Med Rep 21: 1761-1770, 2020
APA
Liu, L., Tan, L., Yao, J., & Yang, L. (2020). Long non‑coding RNA MALAT1 regulates cholesterol accumulation in ox‑LDL‑induced macrophages via the microRNA‑17‑5p/ABCA1 axis. Molecular Medicine Reports, 21, 1761-1770. https://doi.org/10.3892/mmr.2020.10987
MLA
Liu, L., Tan, L., Yao, J., Yang, L."Long non‑coding RNA MALAT1 regulates cholesterol accumulation in ox‑LDL‑induced macrophages via the microRNA‑17‑5p/ABCA1 axis". Molecular Medicine Reports 21.4 (2020): 1761-1770.
Chicago
Liu, L., Tan, L., Yao, J., Yang, L."Long non‑coding RNA MALAT1 regulates cholesterol accumulation in ox‑LDL‑induced macrophages via the microRNA‑17‑5p/ABCA1 axis". Molecular Medicine Reports 21, no. 4 (2020): 1761-1770. https://doi.org/10.3892/mmr.2020.10987