title: The oncogenetic role of microRNA-31 as a potential biomarker in oesophageal squamous cell carcinoma.
abstract: miR-31 (microRNA-31) is frequently altered in numerous cancers. The aim of the present study was to investigate the role of miR-31 in ESCC (oesophageal squamous cell carcinoma). We measured miR-31 in 45 paired ESCC tissues and 523 serum samples using real-time RT (reverse transcription)-PCR. The serum samples were divided into a discovery group (120 ESCCs and 121 normal controls), a validation group (81 ESCCs and 81 controls), and a final group comprising six other common tumours (colorectal, liver, cervical, breast, gastric and lung cancers; total n=120). A Mann-Whitney U test and Wilcoxon matched-pairs test were used for the statistics. miR-31 was up-regulated in 77.8% of the ESCC tissues. Serum miR-31 levels in ESCC patients were significantly higher than in normal controls (P<0.001). It yielded an ROC (receiver operating characteristic) AUC (area under the curve) of 0.902 [95% CI (confidence interval), 0.857-0.936] in the discovery group and a similar result in the validation group [ROC AUC, 0.888 (95% CI, 0.819-0.939)]. Patients with high-levels of serum miR-31 also had a poorer prognosis in relapse-free survival (P=0.001) and tumour-specific survival (P=0.005). In vitro studies showed that miR-31 promoted ESCC colony formation, migration and invasion. Luciferase reporter and Western blot assays confirmed that three tumour suppressor genes, namely EMP1 (epithelial membrane protein 1), KSR2 (kinase suppressor of ras 2) and RGS4 (regulator of G-protein signalling 4), were targeted by miR-31. We conclude that miR-31 plays oncogenetic functions and can serve as a potential diagnostic and prognostic biomarker for ESCC.
authors.affiliation: State Key Laboratory of Molecular Oncology/Department of Etiology & Carcinogenesis, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
authors.forename: Tengfei
authors.initials: T
authors.lastname: Zhang
authors.forename: Qiming
authors.initials: Q
authors.lastname: Wang
authors.forename: Dan
authors.initials: D
authors.lastname: Zhao
authors.forename: Yaling
authors.initials: Y
authors.lastname: Cui
authors.forename: Bangrong
authors.initials: B
authors.lastname: Cao
authors.forename: Liping
authors.initials: L
authors.lastname: Guo
authors.forename: Shih Hsin
authors.initials: SH
authors.lastname: Lu
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000473:pathology / Q000601:surgery; D004812:Epidemiologic Methods; D004938:Esophageal Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000601:surgery; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D012334:RNA, Neoplasm / Q000097:blood / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; C534612:MIRN31 microRNA, human; D035683:MicroRNAs; D012334:RNA, Neoplasm