**4.3 Endogenous and xenobiotics regulation**

The presence of physiological and pathological conditions have been demonstrated to regulate miRNA expression. Previous studies have shown that steroid hormones can regulate miRNA expression [16, 17]. Treatment with estradiol or tamoxifen has been shown significant changes of different miRNAs expressions in patients with breast cancer and in various breast cancer cell lines [16, 17]. In addition, corticosterone also can directly regulate miRNAs expressions [18]. Rats given chronic corticosterone showed significant behavioral disorder associated with differential regulation of 26 miRNAs in the rat prefrontal cortex [18]. Off interesting, those altered miRNAs that were modulated by corticosterone have binding sites for glucocorticoid receptor element (GRE), which were either simple, composite or tethering type within the 1-kb upstream of the transcription start site. These finding suggests that binding with GRE is a common regulatory mechanism of miRNA regulation by corticosterone.

In addition to endogenous regulation, xenobiotics can affect miRNA expression. Increasing evidence from *in vivo* and *in vitro* experiments have showed that specific carcinogen could differentially alter certain miRNAs expressions [19]. Chronic treatment with benzene in mice had showed significant changes in certain miRNAs expressions [20]. Aflatoxin B1, a genotoxic carcinogen, has been reported that it can affect the profile of miRNA expression in different animal models and cell lines [21, 22]. Therefore, miRNAs can serve as biomarkers of toxicity of carcinogen agents and may be useful for early cancer diagnosis. Furthermore, harmful life styles such as alcohol consumption and tobacco smoking can impair miRNAs expressions [23, 24]. Cigarette smoking can change microRNA profile in many human organs and induces the change of plasma miRNA expression profiles in healthy subjects [25, 26]. It has been reported that 24 miRNAs were up-regulated and 11 miRNAs were down-regulated in plasma from smokers [26]. In addition, the serum miRNA profiles in nonsmokers, smokers, and lung-cancer patients were significantly different [24].
