title: MicroRNA drop in the bloodstream and microRNA boost in the tumour caused by treatment with ribonuclease A leads to an attenuation of tumour malignancy.
abstract: Novel data showing an important role of microRNAs in mediating tumour progression opened a new field of possible molecular targets for cytotoxic ribonucleases. Recently, antitumour and antimetastatic activities of pancreatic ribonuclease A were demonstrated and here genome-wide profiles of microRNAs in the tumour and blood of mice bearing Lewis lung carcinoma after treatment with RNase A were analysed by high-throughput Sequencing by Oligonucleotide Ligation and Detection (SOLiD™) sequencing technology. Sequencing data showed that RNase A therapy resulted in the boost of 116 microRNAs in tumour tissue and a significant drop of 137 microRNAs in the bloodstream that were confirmed by qPCR. The microRNA boost in the tumour was accompanied by the overexpression of microRNA processing genes: RNASEN (Drosha), xpo5, dicer1, and eif2c2 (Ago2). Ribonuclease activity of RNase A was shown to be crucial for the activation of both microRNA synthesis and expression of the microRNA processing genes. In the tumour tissue, RNase A caused the upregulation of both oncomirs and tumour-suppressor microRNAs, including microRNAs of the let-7 family, known to negatively regulate tumour progression. Our results suggest that the alteration of microRNA signature caused by RNase A treatment leads to the attenuation of tumour malignancy.
authors.affiliation: Laboratory of Nucleic Acids Biochemistry, Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of Russian Academy of Sciences, Novosibirsk, Russian Federation.
authors.forename: Nadezhda
authors.initials: N
authors.lastname: Mironova
authors.affiliation: Laboratory of Nucleic Acids Biochemistry, Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of Russian Academy of Sciences, Novosibirsk, Russian Federation.
authors.forename: Olga
authors.initials: O
authors.lastname: Patutina
authors.affiliation: Laboratory of Nucleic Acids Biochemistry, Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of Russian Academy of Sciences, Novosibirsk, Russian Federation.
authors.forename: Evgenyi
authors.initials: E
authors.lastname: Brenner
authors.affiliation: Laboratory of Nucleic Acids Biochemistry, Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of Russian Academy of Sciences, Novosibirsk, Russian Federation.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kurilshikov
authors.affiliation: Laboratory of Nucleic Acids Biochemistry, Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of Russian Academy of Sciences, Novosibirsk, Russian Federation.
authors.forename: Valentin
authors.initials: V
authors.lastname: Vlassov
authors.affiliation: Laboratory of Nucleic Acids Biochemistry, Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of Russian Academy of Sciences, Novosibirsk, Russian Federation.
authors.forename: Marina
authors.initials: M
authors.lastname: Zenkova
mesh_terms: D000818:Animals; D018827:Carcinoma, Lewis Lung; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D015723:Gene Library; D051379:Mice; D035683:MicroRNAs / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D008954:Models, Biological; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D015203:Reproducibility of Results; D012259:Ribonuclease, Pancreatic / Q000378:metabolism*; D017422:Sequence Analysis, DNA
chemical_list: D035683:MicroRNAs; D012259:Ribonuclease, Pancreatic