title: Alternative processing of the U2 small nuclear RNA produces a 19-22nt fragment with relevance for the detection of non-small cell lung cancer in human serum.
abstract: RNU2 exists in two functional forms (RNU2-1 and RNU2-2) distinguishable by the presence of a unique 4-bases motif. Detailed investigation of datasets obtained from deep sequencing of five human lung primary tumors revealed that both forms express at a high rate a 19-22nt fragment (miR-U2-1 and -2) from its 3' region and contains the 4-bases motif. Deep sequencing of independent pools of serum samples from healthy donors and lung cancer patients revealed that miR-U2-1 and -2 are pervasively processed in lung tissue by means of endonucleolytic cleavages and stably exported to the blood. Then, microarrays hybridization experiments of matched normal/tumor samples revealed a significant over-expression of miR-U2-1 in 14 of 18 lung primary tumors. Subsequently, qRT-PCR of miR-U2-1 using serum from 62 lung cancer patients and 96 various controls demonstrated that its expression levels identify lung cancer patients with 79% sensitivity and 80% specificity. miR-U2-1 expression correlated with the presence or absence of lung cancer in patients with chronic obstructive pulmonary disease (COPD), other diseases of the lung - not cancer, and in healthy controls. These data suggest that RNU2-1 is a new bi-functional ncRNA that produces a 19-22nt fragment which may be useful in detecting lung cancer non-invasively in high risk patients.
authors.affiliation: Service de Pneumologie, Hôpital Larrey, CHU de Toulouse, Université de Toulouse III, Paul Sabatier, Toulouse, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Mazières
authors.forename: Caroline
authors.initials: C
authors.lastname: Catherinne
authors.forename: Olivier
authors.initials: O
authors.lastname: Delfour
authors.forename: Sandrine
authors.initials: S
authors.lastname: Gouin
authors.forename: Isabelle
authors.initials: I
authors.lastname: Rouquette
authors.forename: Marie-Bernadette
authors.initials: MB
authors.lastname: Delisle
authors.forename: Grégoire
authors.initials: G
authors.lastname: Prévot
authors.forename: Roger
authors.initials: R
authors.lastname: Escamilla
authors.forename: Alain
authors.initials: A
authors.lastname: Didier
authors.forename: David H
authors.initials: DH
authors.lastname: Persing
authors.forename: Mike
authors.initials: M
authors.lastname: Bates
authors.forename: Bernard
authors.initials: B
authors.lastname: Michot
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood* / Q000150:complications / Q000175:diagnosis*; D017931:DNA Primers / Q000235:genetics; D005602:France; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D035683:MicroRNAs / Q000097:blood / Q000235:genetics; D046228:Microarray Analysis / Q000379:methods; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood* / Q000150:complications; D012342:RNA, Small Nuclear / Q000097:blood / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012680:Sensitivity and Specificity
chemical_list: D017931:DNA Primers; D035683:MicroRNAs; D012342:RNA, Small Nuclear; C405484:U2 small nuclear RNA