Blockade of 146b‑5p promotes inflammation in atherosclerosis‑associated foam cell formation by targeting TRAF6

Lin,Nan; An,Yi

doi:10.3892/etm.2017.5121

Blockade of 146b‑5p promotes inflammation in atherosclerosis‑associated foam cell formation by targeting TRAF6

Authors:
- Nan Lin
- Yi An
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Affiliations: Department of Clinical Medicine, Medical College, Qingdao University, Qingdao, Shandong 266021, P.R. China, Division of Cardiology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266100, P.R. China
Published online on: September 18, 2017 https://doi.org/10.3892/etm.2017.5121
Pages: 5087-5092

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Abstract

Atherosclerosis (AS) is a chronic inflammation in response to lipid accumulation. Increasing evidence has demonstrated that numerous microRNAs (miRs) have critical roles in inflammatory responses. A previous study suggested that miR‑146b‑5p is possibly associated with AS; however, its exact role has remained largely elusive. The present study aimed to investigate the potential role of miR‑146b‑5p in AS and to explore the underlying mechanism. Fist, the levels of miR‑146b‑5p were determined in foam cells and clinical specimens from patients with AS by reverse‑transcription quantitative PCR. The role of miR‑146b‑5p in AS was then investigated by using miR‑146b‑5p inhibitor. The results demonstrated that the expression levels of miR‑146b‑5p were elevated in the lesions of patients with AS. In addition, the levels of miR‑146b‑5p in THP‑1 cells stimulated with phorbol 12‑myristate 13‑acetate (100 nM) to induce their differentiation into macrophages were dose‑ and time‑dependently elevated by oxidized low‑density lipoprotein treatment applied for inducing foam cell formation. miR‑146b‑5p was also revealed to directly target tumor necrosis factor receptor‑associated factor 6 (TRAF6), which functions as a signal transducer in the nuclear factor‑κB (NF‑κB) pathway. Furthermore, the present study reported for the first time that miR‑146b‑5p inhibition promotes the inflammatory response and enhances lipid uptake during foam cell formation. In conclusion, miR‑146b‑5p inhibition promoted chronic inflammation and had a detrimental role during AS‑associated foam cell formation by targeting TRAF6.

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