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

Abstract

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.

Inhibition of miR146b‐5p suppresses CT‐guided renal cell carcinoma by targeting TRAF6

“…In this study, we identified TRAF6 as the target of miR146b‐5p in mediating the effects of miR146b‐5p on tumor growth. Our results are consistent with previous reports showing that miR146‐5p targets TRAF6 to regulate relevant cellular functions . It is interesting that miR146‐5p is able to both suppress and promote tumor growth by targeting the same molecular.…”

“…Our results are consistent with previous reports showing that miR146-5p targets TRAF6 to regulate relevant cellular functions. 11,13,16 It is interesting that miR146-5p is able to both suppress and promote tumor growth by targeting the same molecular. In fact, in our study, we also found that TRAF6 knock out mice showed suppressed orthotopic tumor growth to the same extent as treatment of miR146-5p inhibitor in wild type mice.…”

“…One potential mechanism that miR146b‐5p regulates cancer development is through inflammatory response by targeting TRAF6 . However, it is not clear how miR146b‐5p is involved in RCC.…”

“…12 One potential mechanism that miR146b-5p regulates cancer development is through inflammatory response by targeting TRAF6. 13 However, it is not clear how miR146b-5p is involved in RCC. In this current study, we aimed to confirm the upregulation of miR146b-5p in RCC and investigate whether blocking this microRNA was sufficient to suppress renal tumor growth.…”

Molecular mechanisms and genetic regulation in atherosclerosis

“…In addition, miRNA-30e-3p and miRNA-455-3p accelerate vascular inflammation and remodelling by increasing MAPK/NF-κB pathway in rats [ 79 ]. Additionally, up-regulation of miRNA-146b-5p and miRNA-19b increase vascular inflammation and AS via NF-κB activation, foam cell formation, ECM protein synthesis and deposition and plaque formation [ 80 ]. Additionally, downregulation of miRNA-30c-5p promoted macrophage foam cell formation and increased IMT while increased miRNA-30c-5p expression prevented such thickening in human [ 81 ].…”