title: E3 ubiquitin ligase Pirh2 enhances tumorigenic properties of human non-small cell lung carcinoma cells.
abstract: The product ofRCHY1human gene, Pirh2, is a RING-finger containing E3 ligase that modifies p53 with ubiquitin residues resulting in its subsequent degradation in proteasomes. Transcription ofRCHY1is regulated by p53 itself thus forming a negative regulatory feedback loop. Functionally, by eliminating p53, Pirh2 facilitates tumorigenesis. However, the role of Pirh2 in cancer cells lacking p53 is yet not well understood. Therefore, we decided to elucidate the role of Pirh2 in p53-negative human non-small cell lung carcinoma cells, H1299. We found that ectopic expression of Pirh2 enhanced cell proliferation, resistance to doxorubicin, and increased migration potential. Ablation of Pirh2 by specific shRNA reversed these phenotypes. Mechanistically, Pirh2 increased mRNA and protein levels of the c-Myc oncogene. The bioinformatics data indicate that co-expression of both c-Myc and Pirh2 strongly correlated with poor survival of lung cancer patients. Collectively, our results suggest that Pirh2 can be considered as a potential pharmacological target for developing anticancer therapies to treat p53-negative cancers.
authors.affiliation: Institute of Cytology, Russian Academy of Sciences, St Petersburg, Russia.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Daks
authors.affiliation: Institute of Cytology, Russian Academy of Sciences, St Petersburg, Russia.|Almazov Federal North-West Medical Research Centre, Institute of Hematology, St Petersburg, Russia.|National Research University of Information Technologies, Mechanics and Optics, St Petersburg, Russia.
authors.forename: Alexey
authors.initials: A
authors.lastname: Petukhov
authors.affiliation: Institute of Cytology, Russian Academy of Sciences, St Petersburg, Russia.
authors.forename: Olga
authors.initials: O
authors.lastname: Fedorova
authors.affiliation: Institute of Cytology, Russian Academy of Sciences, St Petersburg, Russia.
authors.forename: Oleg
authors.initials: O
authors.lastname: Shuvalov
authors.affiliation: Institute of Cytology, Russian Academy of Sciences, St Petersburg, Russia.
authors.forename: Valeriy
authors.initials: V
authors.lastname: Merkulov
authors.affiliation: Institute of Cytology, Russian Academy of Sciences, St Petersburg, Russia.
authors.forename: Elena
authors.initials: E
authors.lastname: Vasileva
authors.affiliation: MRC Toxicology Unit, Leicester, UK.
authors.forename: Alexey
authors.initials: A
authors.lastname: Antonov
authors.affiliation: Institute of Cytology, Russian Academy of Sciences, St Petersburg, Russia.
authors.forename: Nikolai A
authors.initials: NA
authors.lastname: Barlev
keywords: EMT; H1299; Pirh2; RCHY1; drug resistance; non-small cell lung cancer; xCELLigence