Roles of N-Myc and STAT interactor in cancer: From initiation to dissemination

Pruitt, Hawley C.; Devine, Daniel J.; Samant, Rajeev S.

Indeed, a number of studies have been aimed at elucidating the role of NMI in cancer as summarized in Table 1 . Devine et al. found that NMI protein expression is higher in early stage breast cancer than in later stages, with the lowest expression observed in patients with Stage 4 disease. 4 Moreover, NMI mRNA expression is inversely related to the grade of clinical breast cancer specimens, indicating that the loss of NMI correlates with progression to aggressive disease. Surveys of breast tumor specimens from the Cancer Genome Atlas show little copy number variation or mutation of NMI, yet some independent studies have identified single nucleotide polymorphisms (SNPs) in the NMI gene that are present in breast cancer and ovarian cancer patient samples. 5, 6 Whether these SNPs cause mutations that alter NMI function was not investigated. In contrast to the findings in epithelial cancers, NMI expression in gliomas indicates poor patient prognosis and has been found by Meng et al. to independently predict overall survival and progression-free survival. 7 SNPs in the NMI gene correlated with susceptibility to glioma. These SNPs were identified in the non-coding regions of the NMI gene, and a number of SNPs that conferred risk also increased the activity of the NMI promoter. 8 Furthermore, NMI mRNA and protein was most highly expressed in Grade 4 glioblastoma multiforme (GBM), the most common advanced stage of glioma. 7 Opposing functions of genes in different cancer types has been observed before; and in the case of NMI, the studies of patient specimens show an inverse relationship of the effect of NMI in epithelial cancers versus glial cancers. Taken together, the published literature on NMI suggests that its function can dramatically influence multiple aspects of cancer.