Alteration of microRNA expression in vinyl carbamate-induced mouse lung tumors and modulation by the chemopreventive agent indole-3-carbinol

Abstract

MicroRNAs (miRNAs) are small, non-protein-coding RNAs that can function as tumor suppressors or oncogenes. Deregulation of miRNA expression has been reported in lung cancer. However, modulation of miRNA expression by chemopreventive agents remains to be defined. In the present study, we examined if the chemopreventive agent indole-3-carbinol (I3C) reversed vinyl carbamate (VC)-induced deregulation of miRNA levels in lung tissues of female A/J mice. Lung tissues were obtained from a previous chemoprevention study, in which mice were treated with VC and given I3C in the diet for 15 weeks. Microarray studies revealed alterations in the expression of a number of miRNAs in lung tumors relative to that of normal lungs. miR-21, mir-31, miR-130a, miR-146b and miR-377 were consistently upregulated, whereas miR-1 and miR-143 were downregulated in lung tumors relative to normal lungs. In mice treated with VC and given I3C in the diet, levels of miR-21, mir-31, miR-130a, miR-146b and miR-377 were reduced relative to the level in mice treated with the carcinogen only. The results of the microarray study were confirmed by quantitative reverse transcription-polymerase chain reaction and gel analysis of polymerase chain reaction products. Further studies with miR-21 indicated that phosphatase and tensin homolog, programmed cell death 4 and rich protein with Kazal motifs are potential targets for the oncogenic effect of miR-21 and the chemopreventive activity of I3C. Taken together, we showed here that miRNAs are deregulated during VC-induced mouse lung tumorigenesis and their levels are modulated by I3C. Therefore, miRNAs and their target genes are promising biomarkers for the diagnosis of lung cancer and efficacy of chemopreventive/chemotherapeutic agents.

Potential Chemopreventive Effect Of “Procont”On Mirna Expression In CBA/CA Mice

“…The analysis of miRNAs by microarray method revealed a significant upregulation of miR21, miR31, miR130a and miR146b in lung tumors of mice. While in mice treated with vinyl carbamate and given I3C diet the expression level of these miRNAs were significantly reduced relative to the expression level of mice were treated with vinyl carbamate alone (17). Our study showed parallel results regarding the expression tendency of miR21and miR146a.…”

Growth factor TGF-β induces intestinal epithelial cell (IEC-6) differentiation: miR-146b as a regulatory component in the negative feedback loop

“…For example, up-regulation of miR146b could inhibit the metastasis of breast cancer (Hurst et al 2009), and glioma (Xia et al 2009). A number of other studies observed over-expression of miR-146b in cancer (Melkamu et al 2010;Chen et al 2008;Fulci et al 2009). The stimulatory effect of TGF-b on differentiation of intestinal epithelial cells is closely associated with its tumor suppressing effects; therefore, it is of significance to examine whether and how miR-146b is involved in this important biological process.…”

Resveratrol inhibits glioma cell growth via targeting oncogenic microRNAs and multiple signaling pathways

“…It is well known that small non-coding regulatory RNAs -microRNAs (miRs) are found to be dysregulated in almost all types of cancers and play important roles in cancer development and progression (13)(14)(15)(16)(17). Recent studies have demonstrated that miRs can be regulated by natural agents such as curcumin and Res resulting in suppression of tumor growth, drug resistance and metastasis (18)(19)(20)(21). Our previous studies have confirmed that specific miRs, including miR-21, miR19 and miR-30a-5p are upregulated in GBMs with significant oncogenic activity and their major targeted genes involved in gliomagenesis (22)(23)(24).…”