MiR-27b targets PPARγ to inhibit growth, tumor progression and the inflammatory response in neuroblastoma cells

Abstract

The PPARγ nuclear receptor pathway is involved in cancer, but it appears to have both tumor suppressor and oncogenic functions. In neuroblastoma cells, miR-27b targets the 3′UTR of PPARγ and inhibits its mRNA and protein expression. miR-27b overexpression or PPARγ inhibition blocks cell growth in vitro and tumor growth in mouse xenografts. PPARγ activates expression of the pH regulator NHE1, which is associated with tumor progression. Lastly, miR-27b through PPARγ regulates NF-κB activity and transcription of inflammatory target genes. Thus, in neuroblastoma, miR-27b functions as a tumor suppressor by inhibiting the tumor-promoting function of PPARγ, which triggers an increased inflammatory response. In contrast, in breast cancer cells, PPARγ inhibits NHE1 expression and the inflammatory response, and it functions as a tumor suppressor. We suggest that the ability of PPARγ to promote or suppress tumor formation is linked to cell-type specific differences in regulation of NHE1 and other target genes.

Promising therapeutic role of miR-27b in tumor

“…Reduced expression of oncogene NHE1 which is a downstream protein of PPARγ and decreased NF-κB activity are supposed to contribute to this growth inhibition. 51 6-Gingerol (6G)-induced increased miR-27b suppresses tumor cell proliferation and triggers cell apoptosis of myeloid leukemia through inhibiting PPARγ expression, followed by the suppression of the inflammatory cytokine gene which related to the oncogenic NF-κB pathway. 52 RET is a protooncogene that encodes one of the tyrosine kinase receptors which is involved in signal transduction for hemopoietic cell growth and differentiation.…”

E2F7 regulates transcription and maturation of multiple microRNAs to restrain cell proliferation

“…Several of the miRNAs that we found to be repressed by E2F7 have previously been described as regulators of proliferation pathways (13,14,17,23,24,(52)(53)(54)(55)(56)(57)(58)(59). However, their potential roles in cancer have not been clearly established, as these miRNAs appear to have both oncogenic and antioncogenic functions in different cellular contexts.…”

MicroRNA-27b reverses docetaxel resistance of non-small cell lung carcinoma cells via targeting epithelial growth factor receptor

“…Thereby, suggesting that miR-27b may act as a tumor inhibitor in NSCLC. Previous studies have revealed that miR-27b acts as a tumor suppressor in the development of various malignancies, including prostate cancer, colon cancer and neuroblastoma (24)(25)(26). However, other studies have also indicated that miR-27b may promote tumorigenesis in various cancer types.…”