title: MicroRNA-H4-5p encoded by HSV-1 latency-associated transcript promotes cell proliferation, invasion and cell cycle progression via p16-mediated PI3K-Akt signaling pathway in SHSY5Y cells.
abstract: Herpes simplex virus 1 (HSV-1) microRNAs (miRNAs) mostly located in transcription-associated transcript (LAT) region have been identified that play critical roles in the intricate host-pathogen interaction networks. Increasing evidences throw new insight into the role of miRNA-mediated miRNA-mRNA cross-talk in HSV-1 latent or acute infection. In the present study, we found that hsv-1 miR-H4-5p (here termed as miR-H4b) can down-regulate the expression of cyclin-dependent kinase inhibitor 2A (CDKN2A, p16) in neuroblastoma (SHSY5Y) cell lines. Decreased expression of miR-H4b was directly related to attenuated cell proliferation and invasion as well as malfunction of cell cycle in recombinant SHSY5Y cells that stably expressing miR-H4b. Bioinformatics analysis and luciferase assays demonstrated miR-H4b can directly target p16 mRNA. MiR-H4b exerts its pro-proliferation function through inhibition of the p16-related PI3K-Akt pathways. Our findings provide, for the first time, significant clues regarding the role of herpesvirus-encoded miRNAs as a viral modulator to host cells.
authors.affiliation: Department of Dermatology, The Central Hospital Affiliated to Zhengzhou University Zhengzhou 450007, Henan, PR China.
authors.forename: Huiliang
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Pediatric Surgery, Zhengzhou Children's Hospital Zhengzhou 450053, Henan, PR China.
authors.forename: Chunying
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Pediatric Surgery, Zhengzhou Children's Hospital Zhengzhou 450053, Henan, PR China.
authors.forename: Guangjun
authors.initials: G
authors.lastname: Hou
authors.affiliation: Clinical Laboratory, Zhengzhou Children's Hospital Zhengzhou 450053, Henan, PR China.
authors.forename: Jijun
authors.initials: J
authors.lastname: Song
keywords: Viral microRNA; host-pathogen interaction; p16