title: Knockdown of HMGN5 expression by RNA interference induces cell cycle arrest in human lung cancer cells.
abstract: HMGN5 is a typical member of the HMGN (high mobility group nucleosome-binding protein) family which may function as a nucleosomal binding and transcriptional activating protein. Overexpression of HMGN5 has been observed in several human tumors but its role in tumorigenesis has not been fully clarified. To investigate its significance for human lung cancer progression, we successfully constructed a shRNA expression lentiviral vector in which sense and antisense sequences targeting the human HMGN5 were linked with a 9-nucleotide loop. Inhibitory effects of siRNA on endogenous HMGN5 gene expression and protein synthesis were demonstrated via real-time RT-PCR and western blotting. We found HMGN5 silencing to significantly inhibit A549 and H1299 cell proliferation assessed by MTT, BrdU incorporation and colony formation assays. Furthermore, flow cytometry analysis showed that specific knockdown of HMGN5 slowed down the cell cycle at the G0/G1 phase and decreased the populations of A549 and H1299 cells at the S and G2/M phases. Taken together, these results suggest that HMGN5 is directly involved in regulation cell proliferation in A549 and H1299 cells by influencing signaling pathways involved in cell cycle progression. Thus, our finding suggests that targeting HMGN5 may be an effective strategy for human lung cancer treatment.
authors.affiliation: Department of Respiratory Medicine, The Second Hospital of Jilin University, Changchun, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Chen
authors.forename: Xiu-Li
authors.initials: XL
authors.lastname: Wang
authors.forename: Zhong-Sen
authors.initials: ZS
authors.lastname: Ma
authors.forename: Zhong
authors.initials: Z
authors.lastname: Xu
authors.forename: Bo
authors.initials: B
authors.lastname: Jia
authors.forename: Jin
authors.initials: J
authors.lastname: Ren
authors.forename: Yu-Xin
authors.initials: YX
authors.lastname: Hu
authors.forename: Qing-Hua
authors.initials: QH
authors.lastname: Zhang
authors.forename: Tian-Gang
authors.initials: TG
authors.lastname: Ma
authors.forename: Bing-Di
authors.initials: BD
authors.lastname: Yan
authors.forename: Qing-Zhu
authors.initials: QZ
authors.lastname: Yan
authors.forename: Yan-Lei
authors.initials: YL
authors.lastname: Li
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.forename: Jin-Yan
authors.initials: JY
authors.lastname: Yu
authors.forename: Rong
authors.initials: R
authors.lastname: Gao
authors.forename: Na
authors.initials: N
authors.lastname: Fan
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.forename: Jun-Ling
authors.initials: JL
authors.lastname: Yang
mesh_terms: D002453:Cell Cycle / Q000235:genetics*; D059447:Cell Cycle Checkpoints / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018450:Disease Progression; D015536:Down-Regulation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D024001:HMGN Proteins / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D015534:Trans-Activators / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics*
chemical_list: D024001:HMGN Proteins; C429289:HMGN5 protein, human; D034741:RNA, Small Interfering; D015534:Trans-Activators