The microRNAs as potential biomarkers for predicting the onset of aflatoxin exposure in human beings: a review

Abstract

The identification of aflatoxins as human carcinogens has stimulated extensive research efforts, which continue to the present, to assess potential health hazards resulting from contamination of the human food supply and to minimize exposure. The use of biomarkers that are mechanistically supported by toxicological studies will be important tools for identifying stages in the progression of development of the health effects of environmental agents. miRNAs are small non-coding mRNAs that regulate post-transcriptional gene expression. Also, they are molecular markers of cellular responses to various chemical agents. Growing evidence has demonstrated that environmental chemicals can induce changes in miRNA expression. miRNAs are good biomarkers because they are well defined, chemically uniform, restricted to a manageable number of species, and stable in cells and in the circulation. miRNAs have been used as serological markers of HCC and other tumors. The expression patterns of different miRNAs can distinguish among HCC-hepatitis viruses related, HCC cirrhosis-derivate, and HCC unrelated to either of them. The main objective of this review is to find unreported miRNAs in HCC related to other causes, so that they can be used as specific molecular biomarkers in populations exposed to aflatoxins and as early markers of exposure, damage/presence of HCC. Until today specific miRNAs as markers for aflatoxins-exposure and their reliability are currently lacking. Based on their elucidated mechanisms of action, potential miRNAs that could serve as possible markers of HCC by exposure to aflatoxins are miR-27a, miR-27b, miR-122, miR-148, miR-155, miR-192, miR-214, miR-221, miR-429, and miR-500. Future validation for all of these miRNAs will be needed to assess their prognostic significance and confirm their relationship with the induction of HCC due to aflatoxin exposure.

Involvement of Epigenetics and EMT-Related miRNA in Arsenic-Induced Neoplastic Transformation and Their Potential Clinical Use

“…Furthermore, miRNAs are deregulated by carcinogeneic environmental exposure (78). Some miRNAs are overexpressed or down-regulated exclusively or preferentially in certain cancer types and due to exposure to certain carcinogens (79).…”

The Significance of Regulatory MicroRNAs: Their Roles in Toxicodynamics of Mycotoxins and in the Protection Offered by Dietary Therapeutics Against Mycotoxin‐Induced Toxicity

“…MiR‐130a, miR‐132‐3p, let‐7b, miR‐155, miR‐146a, let‐7d‐5p, miR‐221, miR‐222, and miR‐144 have also been associated with inflammatory gene regulation, and certain human health problems and diseases such as metabolic syndrome, epilepsy, brain injury of intracerebral hemorrhage (Czimmerer et al., ; Marques‐Rocha et al., ; Srivastava, Dixit, Banerjee, Tripathi, & Sarat Chandra, ; Yu et al., ). MiR‐130a, miR‐132, miR‐155, and miR‐221 are found to be able to regulate the toxicity of mycotoxins (Croston, Lemons, Beezhold, & Green, ; Qi et al., ; Valencia‐Quintana et al., ). However, whether or not miRNAs would play a regulatory role in mycotoxin‐induced inflammatory diseases and what specific mechanisms are involved, remain unclear and require furtherinvestigations.…”

“…Since the known molecular mechanisms underlying the pathogenicity and carcinogenicity of mycotoxin are mostly at the protein level, very few examinations on miRNAs (likely the aberrant expressed miRNAs) can be found for early diagnosis of acute toxicity induced by mycotoxin. -122, miR-34a, miR-192, miR-26b, miR-761, miR-21, miR-199a ZEA, AOH, 3-ADON, 15-ADON, AFB1, FB1 (Gazzah et al, 2013;Juan-García et al, 2015;Qian et al, 2016;Girard et al, 2008;Brzuzan et al, 2015;Zhao et al, 2014;Zhou et al, 2016;Amr et al, 2016) Breast cancer miR-21, let-7, miR-200c, miR-199a ZEA, OTA, AFB1, α-ZAL (Yip et al, 2017;Yu et al, 2005;Belhassen et al, 2015;Bian et al, 2017;Elghoroury et al, 2017;Xu et al, 2017) Colon carcinoma miR-378-3a, miR-21, miR-34a, miR-299-3p, miR-495, miR-199a-5p, miR-375, miR-136, miR-15a, miR-192 DON, ZEA (Bensassi et al, 2009;Abassi et al, 2016;Fang et al, 2017;Kara et al, 2015;Wang et al, 2017;Yan et al, 2017;Yuan et al, 2017;Brzuzan et al, 2015) Inflammation-related diseases miR-21, miR-130a, miR-132, miR-155, miR-221 ZEA, DON, OTA, Patulin (Fan et al, 2018;Tardivel et al, 2015;Marin et al, 2017;Kim et al, 2015;McDonald et al, 2015;Croston et al, 2018;Qi et al, 2014;Valencia-Quintana et al, 2014) Apoptosis-induced diseases…”

Evaluating normalization approaches for the better identification of aberrant microRNAs associated with hepatocellular carcinoma

“…Currently, over 100 mature miRNAs have been found to be dysregulated in hepatocellular carcinoma (HCC) tissues or blood. [3,4] Many are also associated with various HCC risk factors, such as hepatitis B/C virus infection, [5,6] aflatoxin B1 exposure, [7] alcohol drinking, non-alcoholic fatty liver disease or non-alcoholic steatohepatitis. [8-10] However, only a small proportion of miRNAs (miR-1, miR-9, miR-16, miR-18a, miR-21, miR-92a, miR-101, miR-122, miR-199a, miR-221, miR-222/223/224, miR-375, miR-483-5p) [11,12] were consistently confirmed by different studies for their role in hepatocarcinogenesis.…”