Acrylamide alters the miRNA profiles and miR‐27a‐5p plays the key role in multiple tissues of rats

Abstract

Acrylamide (AA) is the potential carcinogen, which can induce multiple toxic effects in laboratory animals and humans. So far, increasing attention have been paid to toxical mechanism and intervention measures of AA, however, these details and methods are still obscure. MicroRNAs (miRNAs) have been demonstrated to be involved in toxical functional mechanisms induced by chemicals in vivo or vitro. To explore novel target and mechanism of AA toxicity, a more detailed miRNA expression profiling study is needed. In this study, we established the short‐term high‐dose model of rats with the treatment of 35 mg/kg·b.w./day AA for 17 days, analyzed the miRNAs expression profiling in AA and control groups, and discovered the altered miRNA profiles in 11 tissues with AA treatment. Interestingly enough, the expression of miR‐27a‐5p were significantly up‐regulated in AA group, especially in bladder and hepar. Furthermore, we found miR‐27a‐5p increased in 11 tissues of long‐term low‐dose AA‐treated rats (3.5 mg/kg·b.w./day for 68 days). Therefore, these results revealed that AA changed miRNAs profiles in multiple tissues of SD rats for the first time and suggested that miR‐27a‐5p could be used as the target biomarker for the detection and interference of AA toxicity.

Acrylamide Induces Abnormal mtDNA Expression by Causing Mitochondrial ROS Accumulation, Biogenesis, and Dynamics Disorders

“…To further confirm the results obtained from in vitro study, we measured the changes in oxidative stress and mitochondrial biogenesis-and dynamicsrelated genes in rat brain tissues treated with 35 mg/kg b.w./ day AA for 3 weeks or 10 mg/kg b.w./day AA for 16 weeks. Similar to our previous report, 33 rats treated with 35 mg/kg b.w. /day AA for 3 weeks showed obvious neurotoxic symptoms, abnormal gait, hind limb splay, and weight loss.…”

NF‐κB1 promotes miR‐27a‐5p upregulation in acrylamide‐induced toxicity in rats

“…In this current study, we have successfully demonstrated the association between the transcription factor NF‐κB1 and the promoter region sequences of miR‐27a‐5p, leading to the initiation of gene transcription and activation of target pathways in response to AA treatment both in vivo and in vitro. Our previous research has identified miR‐27a‐5p as a potential biomarker for AA exposure and it induced toxicity through triggering intrinsic apoptosis in rats (Dong et al., 2020; Zhang et al., 2022). Therefore, our findings provide valuable insights into the underlying molecular mechanisms of AA toxicity.…”

The role of microRNAs in acrylamide toxicity

“…Typically, two 21-nucleotide miRNAs with completely comparable base sequences, miR-27a-5p and miR-27a-3p, can be produced from the miR-27a precursor (pre-miR-27a). The miR-21a-30 expression significantly increased in AA-treated rats in six tissues, specifically liver tissue ( 13 ). According to reports, miR-27a-5p and miR-21-3p act together directly to influence the NF-kB signaling axis ( 66 ).…”

“…The AA’s tolerated daily intake (TDI) has been reported to be 2.6 and 40 g/kg/day for carcinogenic and neurotoxic effects, respectively ( 3 , 11 ). Studies on animals and epidemiology have shown that AA, which is classified as a category 2A carcinogen and is thus likely carcinogenic in humans, may have genotoxic, carcinogenic, neurotoxic, and reproductive effects ( 12 , 13 ).…”