Identification of a novel alternatively spliced variant of NADP(H)-dependent retinol dehydrogenase/reductase (NRDR) in cervical squamous carcinoma tissues and clinical significance

Objective: To determine the mRNA and protein expression of NRDRB1,a novel alternatively spliced subtype of NADP(H)-dependent retinol dehydrogenase/reductase(NRDR),in cervical squamous carcinoma tissues and discuss its clinical significance.Methods:RT-PCR,immunofluorescence,immuno-precipitation,immunoblotting,MALDI-TOF mass spectrometry analysis were used to detect NRDRB1 mRNA and protein expression in normal cervical epithelium and cervical squamous carcinoma tissues.Results: The full-length of NRDRB1 subtype was 1171 bp.NRDRB1 protein conserved the coenzyme binding motifs of SDR family at N terminus,substrate binding motifs at C terminus,and peroxisome-targeting signal.NRDRB1 was characterized by a complete deletion of exon 3 which caused the typical loss of LVSNAA-sheet of SDR family and changed the space conformation of NRDRB1 protein,therefore,influenced the cellular localization and function of NRDRB1 protein.The subcellular localization of NRDRB1 was significantly different compared with NRDR.The activity of NRDRB1 was significantly lower than NRDR.NRDRB1 mRNA was detected in 15 of 27(55.6%) cervical squamous carcinoma tissues,significantly higher than that in normal cervical epithelial tissues(P0.05).NRDR were detected in normal cervical epithelium but NRDRB1 mRNA and protein were not.Conclusion: Abnormal alternative splicing of NRDR and the changes of subcellular localization and enzyme activity of a novel spliced subtype NRDRB1 had close association with the initiation and progression of cervical squamous carcinoma.