Epigenetic Mechanisms Involved in Cisplatin-Induced Nephrotoxicity: An Update.

Cisplatin is an antineoplastic drug used for the treatment of many solid tumors. Among its various side effects, nephrotoxicity is the most detrimental. In recent years, epigenetic regulation has emerged as a modulatory mechanism of cisplatin-induced nephrotoxicity, involving non-coding RNAs, DNA methylation and histone modifications. These epigenetic marks alter different signaling pathways leading to damage and cell death. In this review, we describe how different epigenetic modifications alter different pathways leading to cell death by apoptosis, autophagy, necroptosis, among others. The study of epigenetic regulation is still under development, and much research remains to fully determine the epigenetic mechanisms underlying cell death, which will allow leading new strategies for the diagnosis and therapy of this disease.

MicroRNA-33b is a Potential Non-Invasive Biomarker for Response to Atorvastatin Treatment in Chilean Subjects With Hypercholesterolemia: A Pilot Study.

Evidence accumulated so far indicates that circulating levels of microRNAs (miRNAs) are associated with several pathologies. Therefore, differential expression of extracellular miRNAs exhibits promising potential for screening and diagnosis purposes. We evaluated plasma miRNAs in response to the lipid-lowering drug atorvastatin in patients with hypercholesterolemia (HC) and controls. METHODS: We selected miRNAs based on previous data reported by our group and also by employing bioinformatics tools to identify 10 miRNAs related to cholesterol metabolism and statin response genes. Following miRNA identification, we determined plasma levels of miRNA-17-5p, miRNA-30c-5p, miRNA-24-3p, miRNA-33a-5p, miRNA-33b-5p, miRNA-29a-3p, miRNA-29b-3p, miRNA-454-3p, miRNA-590-3p and miRNA-27a-3p in 20 HC patients before and after 1 month of 20 mg/day atorvastatin treatment, evaluating the same miRNA set in a group of 20 healthy subjects, and employing qRT-PCR to determine differential miRNAs expression. RESULTS: HC individuals showed significant overexpression of miRNA-30c-5p and miRNA-29b-3p vs. NL (p = 0.0008 and p = 0.0001, respectively). Once cholesterol-lowering treatment was concluded, HC individuals showed a substantial increase of three extracellular miRNAs (miRNA-24-3p, miRNA-590, and miRNA-33b-5p), the latter elevated more than 37-fold (p = 0.0082). CONCLUSION: Data suggest that circulating miRNA-30c-5p and miRNA-29b-3p are associated with hypercholesterolemia. Also, atorvastatin induces a strong elevation of miRNA-33b-5p levels in HC individuals, which could indicate an important function that this miRNA may exert upon atorvastatin therapy. Additional studies are needed to clarify the role of this particular miRNA in statin treatment.

A New Insight for the Identification of Oncogenic Variants in Breast and Prostate Cancers in Diverse Human Populations, With a Focus on Latinos.

Background: Breast cancer (BRCA) and prostate cancer (PRCA) are the most commonly diagnosed cancer types in Latin American women and men, respectively. Although in recent years large-scale efforts from international consortia have focused on improving precision oncology, a better understanding of genomic features of BRCA and PRCA in developing regions and racial/ethnic minority populations is still required. Methods: To fill in this gap, we performed integrated in silico analyses to elucidate oncogenic variants from BRCA and PRCA driver genes; to calculate their deleteriousness scores and allele frequencies from seven human populations worldwide, including Latinos; and to propose the most effective therapeutic strategies based on precision oncology. Results: We analyzed 339,100 variants belonging to 99 BRCA and 82 PRCA driver genes and identified 18,512 and 15,648 known/predicted oncogenic variants, respectively. Regarding known oncogenic variants, we prioritized the most frequent and deleterious variants of BRCA (n = 230) and PRCA (n = 167) from Latino, African, Ashkenazi Jewish, East Asian, South Asian, European Finnish, and European non-Finnish populations, to incorporate them into pharmacogenomics testing. Lastly, we identified which oncogenic variants may shape the response to anti-cancer therapies, detailing the current status of pharmacogenomics guidelines and clinical trials involved in BRCA and PRCA cancer driver proteins. Conclusion: It is imperative to unify efforts where developing countries might invest in obtaining databases of genomic profiles of their populations, and developed countries might incorporate racial/ethnic minority populations in future clinical trials and cancer researches with the overall objective of fomenting pharmacogenomics in clinical practice and public health policies.

Effect of statins on lipid metabolism-related microRNA expression in HepG2 cells.

BACKGROUND: Statins are potent cholesterol-lowering drugs that prevent cardiovascular events. microRNAs (miRNAs) modulate the expression of genes involved in metabolic pathways and cardiovascular functions post-transcriptionally. This study explored the effects of statins on the expression of miRNAs and their target genes involved in lipid metabolism in HepG2 cells. METHODS: HepG2 cells were treated with atorvastatin or simvastatin (0.1-10 µM) for 24 h. The expression of 84 miRNAs and nine target genes, selected by in silico studies, was measured by qPCR Array and TaqMan-qPCR, respectively. RESULTS: Five miRNAs were upregulated (miR-129, miR-143, miR-205, miR-381 and miR-495) and two downregulated (miR-29b and miR-33a) in atorvastatin-treated HepG2 cells. Simvastatin also downregulated miR-33a expression. Both statins upregulated LDLR, HMGCR, LRP1, and ABCG1, and downregulated FDFT1 and ABCB1, whereas only atorvastatin increased SCAP mRNA levels. In silico analysis of miRNA-mRNA interactions revealed a single network with six miRNAs modulating genes involved in lipogenesis and lipid metabolism. The statin-dysregulated miRNAs were predicted to target genes involved in cellular development and differentiation, regulation of metabolic process and expression of genes involved in inflammation, and lipid metabolism disorders contributing to metabolic and liver diseases. CONCLUSIONS: Atorvastatin-mediated miR-129, miR-143, miR-205, miR-381, and miR-495 upregulation, and miR-29b, and miR-33a downregulation, modulate the expression of target genes involved in lipogenesis and lipid metabolism. Thus, statins may prevent hepatic lipid accumulation and ameliorate dyslipidemia.

Atorvastatin Increases the Expression of Long Non-Coding RNAs ARSR and CHROME in Hypercholesterolemic Patients: A Pilot Study.

Atorvastatin is extensively used to treat hypercholesterolemia. However, the wide interindividual variability observed in response to this drug still needs further elucidation. Nowadays, the biology of long non-coding RNAs (lncRNAs) is better understood, and some of these molecules have been related to cholesterol metabolism. Therefore, they could provide additional information on variability in response to statins. The objective of this research was to evaluate the effect of atorvastatin on three lncRNAs (lncRNA ARSR: Activated in renal cell carcinoma (RCC) with sunitinib resistance, ENST00000424980; lncRNA LASER: lipid associated single nucleotide polymorphism locus, ENSG00000237937; and lncRNA CHROME: cholesterol homeostasis regulator of miRNA expression, ENSG00000223960) associated with genes involved in cholesterol metabolism as predictors of lipid-lowering therapy performance. Twenty hypercholesterolemic patients were treated for four weeks with atorvastatin (20 mg/day). The lipid profile was determined before and after drug administration using conventional assays. The expression of lncRNAs was assessed in peripheral blood samples by RT-qPCR. As expected, atorvastatin improved the lipid profile, decreasing total cholesterol, LDL-C, and the TC/HDL-C ratio (p < 0.0001) while increasing the expression of lncRNAs ARSR and CHROME (p < 0.0001) upon completion of treatment. LASER did not show significant differences among the groups (p = 0.50). Our results indicate that atorvastatin modulates the expression of cholesterol-related lncRNAs differentially, suggesting that these molecules play a role in the variability of response to this drug; however, additional studies are needed to disclose the implication of this differential regulation on statin response.

Circulating miRNA-23b and miRNA-143 Are Potential Biomarkers for In-Stent Restenosis.

In-stent restenosis (ISR) is one of the main complications in patients undergoing percutaneous coronary angioplasty, and microRNAs participate in the contractile-to-synthetic phenotypic switch of vascular smooth muscle cells, a hallmark of restenosis development. MicroRNAs (miRNAs) can be released into circulation from injured tissues, enticing a potential role as noninvasive biomarkers. We aimed to evaluate circulating levels of miRNA-23b, miRNA-143, and miRNA-145 as diagnostic markers of ISR. 142 patients with coronary artery disease undergoing successful angioplasty and a follow-up angiography were included. Subjects were classified according to the degree of obstruction at the angioplasty site into cases (≥50%) or controls (<50%). Total RNA was isolated from plasma to quantify circulating miRNAs levels, and the ROC curves were constructed. Among circulating miRNAs assessed, miRNA-23b and miRNA-143 were significantly lower in cases (miRNA-23b: 18.4x10-5 and miRNA-143: 13.7x10-5) than controls (miRNA-23b: 5.2x10-5, p < 0.0001; miRNA-143: 4.0x10-5, p < 0.0001). Plasma levels of miRNA-145 showed no significant differences. The analysis of the ROC curves showed an area under the curve for miRNA-23b of 0.71 (95% CI: 0.62-0.80, p < 0.0001) and 0.69 for miRNA-143 (95% CI: 0.60-0.78; p < 0.0001). Our data suggest that plasma levels of miRNA-23b and miRNA-143 could be useful as noninvasive biomarkers of ISR.

The Current State of MicroRNAs as Restenosis Biomarkers.

In-stent restenosis corresponds to the diameter reduction of coronary vessels following percutaneous coronary intervention (PCI), an invasive procedure in which a stent is deployed into the coronary arteries, producing profuse neointimal hyperplasia. The reasons for this process to occur still lack a clear answer, which is partly why it remains as a clinically significant problem. As a consequence, there is a vigorous need to identify useful non-invasive biomarkers to differentiate and follow-up subjects at risk of developing restenosis, and due to their extraordinary stability in several bodily fluids, microRNA research has received extensive attention to accomplish this task. This review depicts the current understanding, diagnostic potential and clinical challenges of microRNA molecules as possible blood-based restenosis biomarkers.

Statins differentially modulate microRNAs expression in peripheral cells of hyperlipidemic subjects: A pilot study.

AIM: Although statins are considered a cornerstone for the treatment of high cholesterol levels due to their powerful cholesterol-lowering effects, response to drug administration is still one of the main pitfalls of statin treatment. So far, the reasons underlying this undesired outcome are still poorly understood, but recently, various studies have suggested that miRNAs may be involved. Therefore, we aimed at evaluating the effect of short-term low-dose treatment with 2 statins on miRNAs expression in patients with hypercholesterolemia. METHODS: A total of 40 hypercholesterolemic (HC) subjects following 1 month of atorvastatin (10 mg/day; n = 20) or simvastatin (10 mg/day; n = 20) were included. Multiple available boinformatic algorithms (TargetScan, miRanda, DianaLab, MicroCosm and PicTar) were employed to select miRNAs regulating genes involved in cholesterol metabolism and statin response. Differential miRNAs expression was determined in peripheral cells using the miScript® miRNA PCR Array platform. Pathways involving differentially expressed miRNAs were explored using the Ingenuity Pathway Analysis software. RESULTS: Atorvastatin repressed miR-29a-3p, miR-29b-3p, miR-300, miR-33a-5p, miR-33b-5p and miR-454-3p in HC subjects. On the contrary, simvastatin did not show any effect on miRNAs expression. Network analysis indicated that atorvastatin-modulated miRNAs regulate key cholesterol genes (ABCA1, HMGCR, INSIG1, LDLR, LPL, SCAP and SREBF1). Further subgroups analyses showed that miR-106b-5p, miR-17-3p and miR-590-5p were repressed in HC subjects within the lower quartile of atorvastatin response (lower LDL-C reduction), while the expression of miR-106b-5p, miR-17-3p and miR-183-5p was higher in the upper quartile of simvastatin response (higher LDL-C reduction) (p < 0.05). CONCLUSION: We show that a miRNAs-mediated epigenetic mechanism is differentially affected by statins therapy in vivo, which could be implicated in the variable response to these drugs. Further studies are necessary to disclose their particular role in the cholesterol-reduction response to statins.

Gender-Specific Association Between ABCC2 -24C>T SNP and Reduction in Triglycerides in Chilean Patients Treated With Atorvastatin.

Statins are the first-line therapy prescribed to lower plasma cholesterol levels. Although being safe and showing several beneficial cholesterol-independent pleiotropic effects, a significant variability regarding statin's therapeutic goals has been abundantly documented, but less understood. We aimed to investigate the influence of the ABCC2 -24C>T single nucleotide polymorphism on Chilean hypercholesterolaemic individuals treated for 4 weeks with 10 mg/day atorvastatin. A total of 127 individuals medicated with atorvastatin 10 mg/day/4 weeks were included. Lipid profiles were determined before and after drug administration by conventional assays. Genotyping of the ABCC2 rs717620 SNP (-24C>T) was performed with TaqMan® Drug Metabolism Genotyping Assays. As expected, atorvastatin reduced TC, LDL-C and TG concentrations (p < 0.05). Also, HDL-C levels were increased (p < 0.05). Minor allele frequency for the rs717620 was 0.232. Overall, atorvastatin response was not associated with the ABCC2 rs717620 SNP (p > 0.05). Nonetheless, in male individuals carrying the -24T allele, we observed an attenuated reduction in both TG values and the TG/HDL-C ratio after 10 mg/day atorvastatin. This study indicates that TG levels and the TG/HDL-C ratio are affected by the rs717620 SNP in Chilean males but not female individuals after atorvastatin treatment.

CYP2C19⁎2 Polymorphism in Chilean Patients with In-Stent Restenosis Development and Controls.

Clopidogrel is an antiplatelet drug especially used in patients undergoing percutaneous coronary interventions (PCI). Polymorphisms within CYP2C19 can result in important interindividual variations regarding therapeutic efficacy. Therefore, we aimed to evaluate the impact of the CYP2C19⁎2 variant (rs4244285) on in-stent restenosis occurrence in Chilean patients who underwent PCI and received clopidogrel. A total of 77 cases with stenosis >50% in the angioplasty site (62.75 ± 9.8 years, 80.5% males) and 86 controls (65.45 ± 9.8 years, 72.1% males) were studied. The polymorphism was genotyped using TaqMan® Drug Metabolism Genotyping Assays. Overall, CYP2C19⁎2 allele frequency was 8.3%. Diabetes, chronic lesions, and bare metal stents (BMS) were observed more often in cases than in controls (p = 0.05, p = 0.04, and p = 0.02, resp.). Genotypic frequencies did not differ significantly between the groups (p = 0.15). Nonetheless, the mutated allele was observed in a greater proportion in patients without in-stent restenosis (p = 0.055). There was no significant association between the rs4244285 variant and the occurrence of in-stent restenosis after PCI (OR = 0.44; 95% CI: 0.19 to 1.04; p = 0.06). In summary, no association was identified between the CYP2C19⁎2 variant and the development of coronary in-stent restenosis.

Bacterial Community Profile of the Gut Microbiota Differs between Hypercholesterolemic Subjects and Controls.

The role of gut microbiota in the development of metabolic illnesses has been abundantly demonstrated. Recent studies suggest that gut microbiota alterations may also be related to the development of hypercholesterolemia. Therefore, we aimed to assess differences in the gut bacterial community profiles between hypercholesterolemic subjects and controls. Thirty cases diagnosed with hypercholesterolemia and 27 normocholesterolemic controls were included. A fasting whole blood sample was obtained to determine the lipid profile. In parallel, stool samples were collected and total DNA was isolated to assess the bacterial community profiles by denaturing gradient gel electrophoresis (DGGE). In addition, the Richness, Shannon-Weaver, and Simpson indexes were used to evaluate the richness and diversity of bacterial communities. As expected, serum concentrations of total cholesterol, triglycerides, and LDL-cholesterol were significantly higher in the cases compared with controls. Moreover, DGGE analysis showed a lower richness and diversity of bacterial communities in hypercholesterolemic subjects. In conclusion, our results showed differences in the profiles of bacterial communities between hypercholesterolemic subjects and controls, suggesting a possible role of the gut microbiota in the development of hypercholesterolemia.

Involvement of cytochrome P450 in cisplatin treatment: implications for toxicity.

PURPOSE: The aim of this study is to evaluate the relationship between the CYP450 enzyme family and cisplatin toxicity. METHODS: This article examined a collection of studies suggesting that CYP450 enzymes may influence cisplatin toxicity. We performed a narrative mini-review. RESULTS: The studies review showed that CYP450 enzymes have an important role in drug-induced hepatotoxicity and nephrotoxicity, mainly CYP2E1 and CYP4A11. The studies also suggested that the cisplatin and CYP2E1 interaction leads to the generation of reactive oxygen species (ROS) and other oxidants resulting in renal injury; and that ROS generated by both the use of cisplatin and by the CYP2E1 increases tissue damage, induces apoptosis, and causes liver failure. CONCLUSIONS: We observed that there is an important relationship between CYP450 and cisplatin, involving increased toxicity. However, the possible mechanisms described for the involvement of CYP450 enzymes in nephrotoxicity and hepatotoxicity induced by cisplatin need to be confirmed by further studies. Therefore, there is a need for a deeper investigation focusing on cisplatin toxicity mediated by CYP450 enzymes, which would undoubtedly contribute to a better understanding of the mechanisms that have been implicated so far.

Association of Anxiety-Related Polymorphisms with Sports Performance in Chilean Long Distance Triathletes: A Pilot Study.

Different factors affecting athletic performance are well established: intensity and type of training, anthropometric characteristics as well as an important psychological component. However, the contribution of the genetic background has been less investigated. The aim of the present study was to investigate the influence of polymorphisms within genes associated with stress and anxiety (5HTT, CRH2R, ACE, NK1R, 5HT1AR and CRF-BP) on the physical capability and sports performance in triathletes. One hundred and ninety two (192) unrelated Chilean triathletes who participated in the 2014 70.3 Pucón city triathlon were divided into opposite subgroups of sports performance according to their time results. We identified significant associations for five polymorphisms (5HTT 5-HTTLPR, ACE I/D, NK1R rs6715729, 5HT1AR -1019C>G and CRF-BP CRF-BPs11) with athletic performance. Our results indicate that these polymorphisms are associated with differential sports performance in Chilean triathletes, establishing an initial background for better understanding the relationship between physical performance, genetics and anxiety disorders.

Epigenetic Modifications of Major Depressive Disorder.

Major depressive disorder (MDD) is a chronic disease whose neurological basis and pathophysiology remain poorly understood. Initially, it was proposed that genetic variations were responsible for the development of this disease. Nevertheless, several studies within the last decade have provided evidence suggesting that environmental factors play an important role in MDD pathophysiology. Alterations in epigenetics mechanism, such as DNA methylation, histone modification and microRNA expression could favor MDD advance in response to stressful experiences and environmental factors. The aim of this review is to describe genetic alterations, and particularly altered epigenetic mechanisms, that could be determinants for MDD progress, and how these alterations may arise as useful screening, diagnosis and treatment monitoring biomarkers of depressive disorders.

Polyphenol-Related Epigenetic Modifications in Osteoarthritis: Current Therapeutic Perspectives.

The hyaline cartilage is an avascular, aneural and alymphatic tissue with a limited ability to repair itself. When the cartilage is exposed to some kind of injury, it usually triggers osteoarthritis (OA), a prevalent and degenerative joint disease closely related to aging. OA is both complex and multifactorial, and is the most common form of arthritis, being positioned as a major cause of pain and dysfunction in the world. In addition, high OA prevalence can greatly affect work capacity, making this disease a significant social problem, therefore, its prevention and treatment becomes a priority. At this time, there are numerous therapeutic strategies available to improve hyaline cartilage repair by using chondrocytes or mesenchymal cells, but neither is effective enough to generate functional and durable tissue reparation over time. In OA, chondrocytes have an aberrant gene expression and phenotype, resulting in a loss of balance between anabolic and catabolic processes. Environmental influences such as radiation, infection, smoking, nutrients, toxins and stress can affect gene expression patterns, which may constitute risk factors for various chronic and degenerative diseases, such as OA. In addition, considerable evidence shows that epigenetic mechanisms play an important role in OA chondrogenesis and pathogenesis. Natural plant-derived products such as polyphenols, which are secondary metabolites considered to have potential activity to block inflammation in several degenerative diseases, can stimulate epigenetic modifications, and may provide new therapeutic targets and cost-effective treatments. This review aims to present various polyphenolbased therapies currently used for the treatment of several progressive diseases, including OA.

Polyphenols from Chilean Propolis and Pinocembrin Reduce MMP-9 Gene Expression and Activity in Activated Macrophages.

Polyphenols from diverse sources have shown anti-inflammatory activity. In the context of atherosclerosis, macrophages play important roles including matrix metalloproteinases synthesis involved in degradation of matrix extracellular components affecting the atherosclerotic plaque stability. We prepared a propolis extract and pinocembrin in ethanol solution. Propolis extract was chemically characterized using LC-MS. The effect of treatments on gene expression and proteolytic activity was measured in vitro using murine macrophages activated with LPS. Cellular toxicity associated with both treatments and the vehicle was determined using MTT and apoptosis/necrosis detection assays. MMP-9 gene expression and proteolytic activity were measured using qPCR and zymography, respectively. Thirty-two compounds were identified in the propolis extract, including pinocembrin among its major components. Treatment with either ethanolic extract of propolis or pinocembrin inhibits MMP-9 gene expression in a dose-dependent manner. Similarly, an inhibitory effect was observed in proteolytic activity. However, the effect showed by ethanolic extract of propolis was higher than the effect of pinocembrin, suggesting that MMP-9 inhibition results from a joint contribution between the components of the extract. These data suggest a potential role of polyphenols from Chilean propolis in the control of extracellular matrix degradation in atherosclerotic plaques.

Polyphenol-Rich Extract from Propolis Reduces the Expression and Activity of Streptococcus mutans Glucosyltransferases at Subinhibitory Concentrations.

Tooth decay is an infectious disease, whose main causative agent identified is Streptococcus mutans (S. mutans). Diverse treatments have been used to eradicate this microorganism, including propolis. To date, it has been shown that polyphenols from Chilean propolis inhibit S. mutans growth and biofilm formation. However, the molecular mechanisms underlying this process are unclear. In the present study, we assessed the effect of Chilean propolis on the expression and activity of the glycosyltransferases enzymes and their related genes. Polyphenol-rich extract from propolis inhibited gene expression of glycosyltransferases (GtfB, GtfC, and GtfD) and their related regulatory genes, for example, VicK, VicR, and CcpA. Moreover, the treatment inhibited glucosyltransferases activity measured by the formation of sucrose-derived glucans. Additionally, an inhibitory effect was observed in the expression of SpaP involved in sucrose-independent virulence of S. mutans. In summary, our results suggest that Chilean propolis has a dose-dependent effect on the inhibition of genes involved in S. mutans virulence and adherence through the inhibition of glucosyltransferases, showing an anticariogenic potential of polyphenols from propolis beyond S. mutans growth inhibition.

HMGCR rs17671591 SNP Determines Lower Plasma LDL-C after Atorvastatin Therapy in Chilean Individuals.

Lipid-lowering response to statin therapy shows large interindividual variability. At a genome-wide significance level, single nucleotide polymorphisms (SNPs) in PCSK9 and HMGCR have been implicated in this differential response. However, the influence of these variants is uncertain in the Chilean population. Hence, we aimed to evaluate the contribution of PCSK9 rs7552841 and HMGCR rs17671591 SNPs as genetic determinants of atorvastatin response in Chilean hypercholesterolaemic individuals. One hundred and one hypercholesterolaemic patients received atorvastatin 10 mg/day for 4 weeks. Plasma lipid profile (TC, HDL-C, LDL-C and TG) was determined before and after statin treatment, and SNPs were identified by allelic discrimination using TaqMan(®) SNP Genotyping Assays. Adjusted univariate and multivariate analyses' models were used for statistical analyses, and a p-value <0.05 was considered significant. From baseline (week 0) to the study end-point (week 4), significant reductions were observed in plasma TC, LDL-C and TG (p < 0.001), while HDL-C levels were increased (p < 0.001). Multivariate analysis showed no association between lipid levels and atorvastatin therapy for the PCSK9 variant. However, the HMGCR rs17671591 T allele contributed to basal HDL-C concentration variability along with a higher increase in this lipid fraction after statin medication. In addition, this allele determined greater plasma LDL-C reductions after therapy with atorvastatin. Our data suggest that the HMGCR rs17671591 polymorphism can constitute a genetic marker of lower plasma LDL-C and enhanced HDL-C concentration after atorvastatin therapy in the Chilean population.

Altered microRNome Profiling in Statin-Induced HepG2 Cells: A Pilot Study Identifying Potential new Biomarkers Involved in Lipid-Lowering Treatment.

PURPOSE: Statins are widely prescribed drugs to manage hypercholesterolemia. Despite they are considered effective lipid-lowering agents, significant inter-individual variability has been reported in relation to drug response. Among the reasons explaining this variation, genetic factors are known to partially contribute. Nonetheless, poor evidence exists regarding epigenetic factors involved. METHODS: We investigated if atorvastatin can modulate the cholesterol related miR-33 family. Furthermore, we analyzed the microRNA expression profiles in HepG2 cells treated for 24 hours with atorvastatin or simvastatin using a microarray platform. RESULTS: Our results indicate that atorvastatin does not influence the expression of the miR-33 family. In addition, microarray examination revealed that atorvastatin modulated thirteen miRs, whilst simvastatin only affected two miRs. All significantly modulated miRs after simvastastin therapy were also modulated by atorvastatin. In addition, four novel miRs with previously unreported functions were identified as statin-modulated. CONCLUSION: We identified several novel miRs affected by statin treatment. Additional research is needed to determine the biological significance of differentially expressed miRs identified in statins-induced HepG2 cells.