The miR-17/92 cluster is among the best-studied microRNA clusters. Interest in the cluster and its members has been increasing steadily and the number of publications has grown exponentially since its discovery with more than 1000 articles published in 2012 alone. Originally found to be involved in tumorigenesis, research work in recent years has uncovered unexpected roles for its members in a wide variety of settings that include normal development, immune diseases, cardiovascular diseases, neurodegenerative diseases and aging. In light of its ever-increasing importance and ever-widening regulatory roles, we review here the latest body of knowledge on the cluster's involvement in health and disease as well as provide a novel perspective on the full spectrum of protein-coding and non-coding transcripts that are likely regulated by its members.

Three commercial Lyme disease Western immunoblotting (WB) kits and the C6 Borrelia burgdorferi (Lyme) enzyme-linked immunosorbent assay (ELISA) kit were compared using two commercially available performance panels from the Centers for Disease Control and Prevention (CDC) and Boston Biomedica (BBI). Combined, the panels consisted of 52 characterized specimens. Immunoglobulin G (IgG) sensitivity was similar for the three WB products. The BBI and Marblot WBs were more specific for IgG antibodies, while the Virablot was the most sensitive for IgM antibody. The BBI WB was 100% specific for IgM, while Marblot was 97% and Virablot was 77% specific for IgM. The C6 ELISA was found to be 100% sensitive. Four false-positive C6 results were identified in patients that had clinically and microbiologically confirmed Lyme disease but were not detected by the CDC reference methods. No one WB product showed overall superiority. The C6 ELISA shows promise as the first ELISA for Lyme disease that would not require a supplemental test such as a WB.Early tests for the serological detection of Borrelia burgdorferi antibodies in patients suspected of having Lyme disease (LD) lacked both sensitivity and specificity (1, 5). (11) evaluated the available WB kits by using commercially available performance panels and reported differences in specificities and sensitivities. That study and the present one were, in part, a response to the recommendations of the CDC-AST-PHLD Dearborn Conference participants, who stated that (i) LD testing should only be performed in laboratories with comprehensive quality control systems, (ii) serum samples used to evaluate diagnostic products should cover all stages of LD, and (iii) a repository of characterized specimens should be available for comparative testing of diagnostic products for LD (2).There have been no reports on the performance of confirmatory serological tests for LD since 1998. Tilton recently reviewed new serological tests for LD (10), and although substantial progress toward the sensitive and specific detection of immunoglobulin G (IgG) and IgM antibodies to B. burgdorferi has been made, there is presently no definitive evidence that any of these tests are capable of being stand-alone tests with no confirmatory or supplemental WB. Some of these tests, such as the C6 Lyme antibody test (8) and the VlsE antibody test (6), show promise because of their high specificity and acceptable sensitivity in all stages of the disease.As of early 2004, three Lyme WB products were available in the United States: the Marblot (MarDx, Carlsbad, Calif.), the Boston Biomedica (BBI; West Bridgewater, Mass.) WB test kit, and the Virablot (Viramed, Steinkirchen, Germany). Two other products, QualiCode (Immunetics, Cambridge, Mass.) and a WB kit from Focus Technologies (Cypress, Calif.) were unavailable because of reformatting and withdrawal from the market, respectively. Of the three available products, two (Marblot and the BBI kit) are FDA approved. The Virablot kit is for research purposes only pending FDA re...

Breast cancer type 2, early onset susceptibility gene (BRCA2) is a major component of the homologous recombination DNA repair pathway. It acts as a tumor suppressor whose function is often lost in cancers. Patients with specific mutations in the BRCA2 gene often display discrete clinical, histopathological, and molecular features. However, a subset of sporadic cancers has wild type BRCA2 and display defects in the homology-directed repair pathway, which is the hallmark of ‘BRCAness.’ The mechanisms by which BRCAness arises are not well understood but post-transcriptional regulation of BRCA2 gene expression by microRNAs (miRNAs) may contribute to this phenotype. Here, we examine the post-transcriptional effects that some members of the six-miRNA cluster known as the miR-17/92 cluster have on the abundance of BRCA2’s messenger RNA (mRNA) and protein. We discuss two interactions involving the miR-19a and miR-19b members of the cluster and the 3′UTR of BRCA2’s mRNA. We investigated these miRNA:mRNA interactions in 15 cell lines derived from pancreatic, breast, colon, and kidney tissue. We show that over-expression of these two miRNAs results in a concomitant decrease of BRCA2’s mRNA and protein expression in a subset of the tested cell lines. Additionally, using luciferase reporter assays we identified direct interactions between miR-19a/miR-19b and a miRNA response element (MRE) in BRCA2’s 3′UTR. Our results suggest that BRCA2 is subject to a complex post-transcriptional regulatory program that has specific dependencies on the genetic and phenotypic background of cell types.