Effect of 7,12-Dimethylbenz(α)anthracene on the Expression of miR-330, miR-29a, miR-9-1, miR-9-3 and the mTORC1 Gene in CBA/Ca Mice

Abstract

Background/Aim: Development of malignant tumors is preceded by molecular biological events. Our aim was to establish an assay panel by using miRNAs and other genes for the rapid screening of potential carcinogens or chemopreventive agents. Materials and Methods: Six male and 6 female CBA/Ca mice received 20 mg/bwkg 7,12dimethylbenz(α)anthracene (DMBA) intraperitoneally, and 24 h later RNA was isolated from parenchymal organs. Expression of miR-330, miR-29a, miR-9-1, miR-9-3 and mTORC1 was analysed by real time polymerase chain reaction and compared to non-treated controls. Results: DMBA caused significant alterations in the expression of the studied genes. The most profound changes were the strongly elevated miR-9-3 and mTORC1 expressions in female mice in all organs studied. Conclusion: miR-9-3 and mTORC1 expression in female mice were found to be the most suitable biomarkers for rapid identification of possible carcinogenic effects. According to estimates, in 2018 there were 18.1 million new malignant cancer cases and 9.6 million cancer deaths (1). According to WHO data, 30-50 % of all malignant tumors could be prevented (2), and early diagnosis would usually increase the chance of successful treatment.

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

“…Both DMBA treatment and DMBA added combined with TFA caused significant L1-RTP DNA hypomethylation in the liver, spleen, and kidneys of CBA/Ca mice. According to the literature, DMBA forms DNA adducts and thereby inhibits tumor suppressor genes (for example, P53), activates oncogenes (for example, RAS, C-MYC, BCL-2, NOTCH), and alters microRNA (for example miR-9, miR-124, miR-132; miR-134) patterns leading to global hypomethylation [29,31,52,67,93,154].…”

“…DMBA also significantly elevated mTORC1 gene expression and miR-9 level in the liver, spleen, and kidneys of CBA/CA female mice, compared to untreated controls [93]. DMBA activates the enzymes of glycolysis and lipogenesis [77].…”

“…However, increased activity of both mTOR and HIF-1 reduces life expectancy [96,97]. The expression level of miR-9 is increased by C-MYC, and miR-9 inhibits the progression of HCC as a tumor suppressor, but miR-9 also amplifies E-cadherin, which increases C-MYC expression, which increases miR-9 level, forming a positive feedback loop [93,98].…”

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

“…Tomesz et al, and we examined the expression of miR-134, miR-132, miR-124-1, miR-9-3, and of mTOR in the liver, spleen and kidney of 7,12-dimethylbenz [a] anthracene (DMBA) treated mice as molecular epidemiological biomarkers [26]. The effect of DMBA damage is indicated by an increase both in the expression of these miRs and in the expression of mTOR, among other, in the examined organs, since DMBA is a pluripotent carcinogen, while induces mutations and increases the expression of oncogenes, etc.…”

“…The effect of DMBA damage is indicated by an increase both in the expression of these miRs and in the expression of mTOR, among other, in the examined organs, since DMBA is a pluripotent carcinogen, while induces mutations and increases the expression of oncogenes, etc. [26]. The aim of our research was to explore the expression patterns of these miRs so that we can follow the harmful and beneficial tumor biological effects of TFA and olive oil.…”