title: Site-specific RNase A activity was dramatically reduced in serum from multiple types of cancer patients.
abstract: Potent RNase activities were found in the serum of mammals but the physiological function of the RNases was never well illustrated, largely due to the caveats in methods of RNase activity measurement. None of the existing methods can distinguish between RNases with different target specificities. A systematic study was recently carried out in our lab to investigate the site-specificity of serum RNases on double-stranded RNA substrates, and found that serum RNases cleave double-stranded RNAs predominantly at 5'-U/A-3' and 5'-C/A-3' dinucleotide sites, in a manner closely resembling RNase A. Based on this finding, a FRET assay was developed in the current study to measure this site-specific serum RNase activity in human samples using a double stranded RNA substrate. We demonstrated that the method has a dynamic range of 10(-5) mg/ml- 10(-1) mg/ml using serial dilution of RNase A. The sera of 303 cancer patients were subjected to comparison with 128 healthy controls, and it was found that serum RNase activities visualized with this site-specific double stranded probe were found to be significantly reduced in patients with gastric cancer, liver cancer, pancreatic cancer, esophageal cancer, ovary cancer, cervical cancer, bladder cancer, kidney cancer and lung cancer, while only minor changes were found in breast and colon cancer patients. This is the first report using double stranded RNA as probe to quantify site-specific activities of RNase A in a serum. The results illustrated that RNase A might be further evaluated to determine if it can serve as a new class of biomarkers for certain cancer types.
authors.affiliation: Institute of Molecular Medicine, Peking University, Beijing, People's Republic of China.
authors.forename: Weiyan
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Etiology and Carcinogenesis and State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Mei
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Institute of Molecular Medicine, Peking University, Beijing, People's Republic of China.
authors.forename: Na
authors.initials: N
authors.lastname: Wei
authors.affiliation: Institute of Molecular Medicine, Peking University, Beijing, People's Republic of China.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Wang
authors.affiliation: Institute of Molecular Medicine, Peking University, Beijing, People's Republic of China.
authors.forename: Huqing
authors.initials: H
authors.lastname: Cao
authors.affiliation: Institute of Molecular Medicine, and the State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, People's Republic of China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Du
authors.affiliation: Institute of Molecular Medicine, Peking University, Beijing, People's Republic of China.
authors.forename: Zicai
authors.initials: Z
authors.lastname: Liang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000201:enzymology*; D012260:Ribonucleases / Q000378:metabolism*; D055815:Young Adult
chemical_list: D012260:Ribonucleases