In vivo effects of olive oil and trans-fatty acids on miR-134, miR-132, miR-124-1, miR-9-3 and mTORC1 gene expression in a DMBA-treated mouse model

Abstract

Both the intake of beneficial olive oil and of harmful trans-fatty acids (TFAs) in consumed foods are of great significance in tumor biology. In our present study we examined the effects they exert on the expression patterns of miR-134, miR-132, miR-124-1, miR-9-3 and mTOR in the liver, spleen and kidney of mice treated with 7,12-dimethylbenz [a] anthracene (DMBA). Feeding of TFA-containing diet significantly increased the expression of all studied miRs and mTORC1 in all organs examined, except the expression of mTORC1 in the spleen and kidney. Diet containing olive oil significantly reduced the expression of miR-124-1, miR-9-3 and mTORC1 in the liver and spleen. In the kidney, apart from the mTORC1 gene, the expression of all miRs examined significantly decreased compared to the DMBA control. According to our results, the cell membrane protective, antioxidant, and anti-inflammatory effects of olive oil and the cell membrane damaging, inflammatory, and carcinogenic properties of TFA suggest negative feedback regulatory mechanisms. In contrast to our expectations, mTORC1 gene expression in the kidney has not been shown to be an appropriate biomarker–presumably, because the many complex effects that regulate mTOR expression may quench each other.

The potential of lunasin extract for the prevention of breast cancer progression by upregulating E-Cadherin and inhibiting ICAM-1

“…31 Several studies have also investigated DMBA as a tumor model and discovered a significant increase in ICAM-1 expression. [32][33][34] Although the evidence is inconclusive, the nuclear factor-kappaB (NFkB) pathway is considered to play a role in DMBA-induced ICAM-1 upregulation. 35,36 DMBA is able to potentiate NFkB 37,38 via Ras mutation in the Ras/Raf/ mitogen-activated protein kinase/ERK kinase (MEK)/extracellular-signal-regulated kinase (ERK) pathway, 39,40 thereby increasing ICAM-1 expression.…”

Olive Oil: Nutritional Applications, Beneficial Health Aspects and its Prospective Application in Poultry Production

“…EVOO is much resistance to high temperatures and contains essential antioxidant compounds which scavenge free radicals, hence perform potent anti-inflammatory actions ( Dick, 2018 ). In vivo study by Molnar et al (2021) stated that olive oil at a dose of 0.3 g/animal/day had the cell membrane protective and anti-inflammatory effects. Due to its effective anti-inflammatory action, regular intake of olive oil has shown provide relief rheumatoid arthritis, which is an autoimmune disease characterized by inflammation and pain of joints ( Wahle, 2004 ).…”

Olive Oil Improves While Trans Fatty Acids Further Aggravate the Hypomethylation of LINE-1 Retrotransposon DNA in an Environmental Carcinogen Model

“…These oxidative and inflammatory damages are added to the effects of DMBA as mentioned earlier [55]. The cell membrane fluidity enhancing effects of MUFA and PUFA promote DNA methylation via the above-mentioned secondary signaling pathways (for example by decreasing NF-κB) [67,103]. Theoretically, the saturated fatty acids, due to their membrane rigidity enhancing effects [104], could cause hypomethylation of L1-RTP DNA.…”

“…ROS also exerts harmful effects by activating secondary signaling pathways, for example, increases levels of interleukin 1β (IL1β), interleukin 6 (IL6), and tumor necrosis factor (TNF), and stimulates nuclear factor kappa B (NF-κB) [64,65], which indirectly increases the likelihood of malignant transformation [31,[65][66][67], and is also directly proinflammatory [64,68,69]. TNF-α through IFN activation causes global DNA hypomethylation in aging cells [49,70].…”

“…DMBA also activates the mitogen-activated protein kinase (MAPK) and Janus kinase (JAK) secondary signaling pathways [76], which activates the above-mentioned interleukins (and consequently NF-κB). These processes finally lead to global DNA hypomethylation [31] and accelerate aging, for example, by decreasing the expression of antitumorigenic microRNA-134 (miR-134) and P53 [67,75,[90][91][92].…”