Age-dependent alteration of microRNAs related to brain cancer in C6 glioma cells and young and old hippocampal rats after exposure to 1,2-Diacetylbenzene

Objective 1,2-Diacetylbenzene (DAB) induces cognitive and motor deficits, which are the most common symptoms of cancer (e.g., glioma), and gene expression plays an important regulatory role during the progression of memory and motor deficits. We aimed to assess the expression patterns and molecular activities of miRNAs in rats exposed to DAB. Methods We compared miRNA expressions in the hippocampal tissues of DAB-treated young and old rats with those in treatment-naive young or old controls as well as BV2 microglial cells and C6 cells to provide functional evidence of miRNA differences in young and old rats and to access molecular processes. miRNA expression profiles were obtained by microarray analysis and were confirmed by quantitative RT-PCR. Gene ontology, KEGG enrichment analyses, and MIENTURNET were performed on genes targeted by miRNAs. Results Twelve miRNAs were found to be differentially expressed (8 upregulated and 4 downregulated) in young DABtreated rats versus non-treated young rats, while 10 miRNAs (7 upregulated and 3 downregulated) were differentially expressed in old DAB-treated rats versus non-treated old rats. Expressions of miR-200a-3p, miR- 200b-3p, and miR-429 were significantly higher in young DAB-treated rats than in non-treated young rats, and those of miR-196a-5p and miR224-5p were significantly higher in old DAB-treated rats than in non-treated old rats (p < 0.001). rno-miR-200a- 3p, rnomiR-200b-3p, rno-miR- 200c- 3p & rno-miR-141-3p were involved in glioma-related genes (Zeb1 and 2). Furthermore, the expression levels of these miRNAs were significantly increased in C6 cells treated with DAB compared with non-treated C6 and BV2 microglial cells. In silico analyses showed that these miRNAs are associated with glioma-related pathways. Elevated miR-200a family and miR-196a expressions may play an important role in the development of glioma-induced memory and motor deficits. Conclusions Further work is needed to confirm whether this dose of DAB would eventually induce gliomas near the hippocampus and might manifest cognitive and motor deficits. [Graphics] .

Automated summary

This study assessed the expression patterns and molecular activities of miRNAs in rats exposed to 1,2-Diacetylbenzene (DAB). The results showed differential expression of miRNAs in young and old DAB-treated rats compared to non-treated rats. The elevated expression of miR-200a family and miR-196a may play an important role in the development of glioma-induced memory and motor deficits.