Long non‑coding RNA AL355711 promotes smooth muscle cell migration through the ABCG1/MMP3 pathway

Int J Mol Med. 2021 Dec;48(6):207. doi: 10.3892/ijmm.2021.5040. Epub 2021 Oct 5.

Abstract

Atherosclerosis and related cardiovascular diseases pose severe threats to human health worldwide. There is evidence to suggest that at least 50% of foam cells in atheromas are derived from vascular smooth muscle cells (VSMCs); the first step in this process involves migration to human atherosclerotic lesions. Long non‑coding RNAs (lncRNAs) have been found to play significant roles in diverse biological processes. The present study aimed to investigate the role of lncRNAs in VSMCs. The expression of lncRNAs or mRNAs was detected using reverse transcription‑quantitative polymerase chain reaction. The Gene Expression Omnibus datasets in the NCBI portal were searched using the key words 'Atherosclerosis AND tissue AND Homo sapiens' and the GSE12288 dataset. Gene expression in circulating leukocytes was measured to identify patients with coronary artery disease (CAD) or controls, and used to analyze the correlation coefficient and expression profiles. The protein level of ATP‑binding cassette sub‑family G member 1 (ABCG1) and matrix metalloproteinase (MMP)3 was determined using immunohistochemistry and western blot analysis. The analysis of mouse aortic roots was performed using Masson's and Oil Red O staining. The expression of lncRNA AL355711, ABCG1 and MMP3 was found to be higher in human atherosclerotic plaques or in patients with atherosclerotic CAD. The correlation analysis revealed that ABCG1 may be involved in the regulation between lncRNA AL355711 and MMP3 in atherosclerotic CAD. The knockdown of lncRNA AL355711 inhibited ABCG1 transcription and smooth muscle cell migration. In addition, lncRNA AL355711 was found to regulate MMP3 expression through the ABCG1 pathway. The expression of ABCG1 and MMP3 was found to be high in an animal model of atherosclerosis. The results indicated that lncRNA AL355711 promoted VSMC migration and atherosclerosis partly via the ABCG1/MMP3 pathway. On the whole, the present study demonstrates that the inhibition of lncRNA AL355711 may serve as a novel therapeutic target for atherosclerosis. lncRNA AL355711 in circulating leukocytes may be a novel biomarker for atherosclerotic CAD.

Keywords: ATP‑binding cassette sub‑family G member 1; Vascular smooth muscle cell migration; atherosclerosis; long non‑coding RNA AL355711; matrix metalloproteinase 3.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 1 / genetics*
  • ATP Binding Cassette Transporter, Subfamily G, Member 1 / metabolism
  • Animals
  • Atherosclerosis / genetics
  • Atherosclerosis / pathology
  • Cell Movement / genetics
  • Cells, Cultured
  • Disease Models, Animal
  • Gene Expression Regulation
  • Humans
  • Male
  • Matrix Metalloproteinase 3 / genetics
  • Matrix Metalloproteinase 3 / metabolism*
  • Metabolic Networks and Pathways / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout, ApoE
  • Myocytes, Smooth Muscle / cytology
  • Myocytes, Smooth Muscle / pathology
  • Myocytes, Smooth Muscle / physiology*
  • Plaque, Atherosclerotic / genetics*
  • Plaque, Atherosclerotic / metabolism
  • Plaque, Atherosclerotic / pathology
  • RNA, Long Noncoding / genetics*

Substances

  • ABCG1 protein, human
  • ABCG1 protein, mouse
  • ATP Binding Cassette Transporter, Subfamily G, Member 1
  • RNA, Long Noncoding
  • MMP3 protein, human
  • Matrix Metalloproteinase 3
  • Mmp3 protein, mouse

Grants and funding

The present study was supported by grants from the National Natural Sciences Foundation of China (grant no. 82072336), the Natural Science Fund of Guangdong (grant nos. 2019A1515010178 and 2019B1515120004), the Science and Technology Program of Guangzhou (grant nos. 202002020038, 202102010173 and 202103000025), the Medical Scientific Research Foundation of Guangdong Province of China (grant nos. A2019282 and A2020108) and the Project of Administration of Traditional Chinese Medicine of Guangdong Province of China (grant no. 20211180).