406901

MIR107

MIRN107|miR-107;microRNA 107;MIR107;microRNA 107

hsa-mir-107

10q23.31

ncRNA

microRNAs (miRNAs) influence many biological processes, including cancer. They do so by posttranscriptionally repressing target mRNAs to which they have sequence complementarity. Although it has been postulated that miRNAs can regulate other miRNAs, this has never been shown experimentally to our knowledge. Here, we demonstrate that miR-107 negatively regulates the tumor suppressor miRNA let-7 via a direct interaction. miR-107 was found to be highly expressed in malignant tissue from patients with advanced breast cancer, and its expression was inversely correlated with let-7 expression in tumors and in cancer cell lines. Ectopic expression of miR-107 in human cancer cell lines led to destabilization of mature let-7, increased expression of let-7 targets, and increased malignant phenotypes. In contrast, depletion of endogenous miR-107 dramatically increased the stability of mature let-7 and led to downregulation of let-7 targets. Accordingly, miR-107 expression increased the tumorigenic and metastatic potential of a human breast cancer cell line in mice via inhibition of let-7 and upregulation of let-7 targets. By mutating individual sites within miR-107 and let-7, we found that miR-107 directly interacts with let-7 and that the internal loop of the let-7/miR-107 duplex is critical for repression of let-7 expression. Altogether, we have identified an oncogenic role for miR-107 and provide evidence of a transregulational interaction among miRNAs in human cancer development.

Abnormal microRNA (miRNA) expression profiles have recently been associated with sporadic pituitary adenomas, suggesting that miRNAs can contribute to tumor formation; miRNAs are small noncoding RNAs that inhibit posttranscriptional expression of target mRNAs by binding to target sequences usually located in the 3-UTR. In this study, we investigated the role played by miR-107, a miRNA associated with different human cancers, in sporadic pituitary adenomas and its interaction with the pituitary tumor suppressor gene aryl hydrocarbon receptor-interacting protein (AIP). miR-107 expression was evaluated in pituitary adenoma and normal pituitary samples using microRNA screen TLDA (TaqMan Low-Density Array) and RT-qPCR assays. We show that miR-107 expression was significantly upregulated in GH-secreting and nonfunctioning pituitary adenomas. We found that human AIP-3-UTR is a target of miR-107 since miR-107 inhibited in vitro AIP expression to 53.9 +/- 2% of the miRNA control in a luciferase assay and reduced endogenous AIP mRNA expression to 53 +/- 22% of the miRNA control in human cells. However, we did not observe a negative correlation between AIP and miR-107 expression in the human tumor samples. Furthermore, we show that miR-107 overexpression inhibited cell proliferation in human neuroblastoma and rat pituitary adenoma cells. In conclusion, miR-107 is overexpressed in pituitary adenomas and may act as a tumor suppressor. We have identified and confirmed AIP as a miR-107 target gene. expression data in human samples suggest that the expression of AIP and miR-107 could be influenced by a combination of tumorigenic factors as well as compensatory mechanisms stimulated by the tumorigenic process.

microRNAs (miRNAs) are small noncoding RNAs that function as tumor suppressors or oncogenes. microRNA-107 (miR-107), a transcriptional target of p53, is deregulated in many cancer cell lines. Here, we showed that miR-107 is down-regulated in glioma tissues and cell lines, in particular, p53-mutated U251 and A172. Transfection of wild-type p53 into these cells stimulated miR-107 expression. To investigate the role of miR-107 in tumorigenesis, we constructed a lentiviral vector overexpressing miR-107. Notably, miR-107 inhibited proliferation and arrested the cell cycle at the G0-G1 phase in glioma cells. Transduction of Lenti-GFP-miR-107 into glioma cells inhibited CDK6 and Notch-2 protein expression. Our findings collectively demonstrate that p53-induced miR-107 suppresses brain tumor cell growth and down-regulates CDK6 and Notch-2 expression, supporting its tumor suppressor role and utility as a target for glioma therapy.