title: RETRACTED: Silencing of Kv1.5 Gene Inhibits Proliferation and Induces Apoptosis of Osteosarcoma Cells.
abstract: Kv1.5 (also known as KCNA5) is a protein encoded by the KCNA5 gene, which belongs to the voltage-gated potassium channel, shaker-related subfamily. Recently, a number of studies have suggested that Kv1.5 is overexpressed in numerous cancers and plays crucial roles in cancer development. However, until now, the expression and functions of Kv1.5 in osteosarcoma are still unclear. To characterize the potential biological functions of Kv1.5 in osteosarcoma, herein, we examined the expression levels of Kv1.5 in osteosarcoma cells and tissues using quantitative real-time polymerase chain reaction (qRT-PCR), western blot, and immunohistochemistry assays. Four short hairpin RNAs (shRNAs) targeting Kv1.5 were designed and homologous recombination technology was used to construct pGeneSil-Kv1.5 vectors. In addition, the vectors were transfected into osteosarcoma MG63 cells and Kv1.5 mRNA level was measured by qRT-PCR and the Kv1.5 protein level was examined by western blot. We also examined the effects of Kv1.5 silencing on proliferation, cell cycle and apoptosis of the osteosarcoma cells using CCK-8, colony formation, flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays. Our results showed that Kv1.5 was aberrantly expressed in osteosarcoma and that the synthesized shRNA targeting Kv1.5 reduced Kv1.5 mRNA and protein expression effectively. Silencing Kv1.5 expression in the osteosarcoma cells significantly inhibited the proliferation of osteosarcoma cells, induced cell cycle arrest at G0/G1 phase, and induced cell apoptosis through up-regulation of p21, p27, Bax, Bcl-XL and caspase-3 and down-regulation of cyclins A, cyclins D1, cyclins E, Bcl-2 and Bik. In summary, our results indicate that Kv1.5 silencing could suppress osteosarcoma progression through multiple signaling pathways and suggest that Kv1.5 may be a novel target for osteosarcoma therapeutics.
authors.affiliation: Department of Orthopaedics, the Affiliated Southeast Hospital of Xiamen University, Orthopaedic Center of People's Liberation Army, Zhangzhou 363000, China. wu215@iupui.edu.
authors.forename: Jin
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Orthopaedics, the Affiliated Southeast Hospital of Xiamen University, Orthopaedic Center of People's Liberation Army, Zhangzhou 363000, China. chenzhida175th@gmail.com.
authors.forename: Zhida
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Orthopaedics, the Affiliated Southeast Hospital of Xiamen University, Orthopaedic Center of People's Liberation Army, Zhangzhou 363000, China. liuqingjun175th@gmail.com.
authors.forename: Qingjun
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Orthopaedics, the Affiliated Southeast Hospital of Xiamen University, Orthopaedic Center of People's Liberation Army, Zhangzhou 363000, China. zengwenrong175th@gmail.com.
authors.forename: Wenrong
authors.initials: W
authors.lastname: Zeng
authors.affiliation: Department of Neurology, the Affiliated Southeast Hospital of Xiamen University, Zhangzhou 363000, China. wujinzi1983@gmail.com.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Orthopaedics, the Affiliated Southeast Hospital of Xiamen University, Orthopaedic Center of People's Liberation Army, Zhangzhou 363000, China. linbin175th@gmail.com.
authors.forename: Bin
authors.initials: B
authors.lastname: Lin
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D001859:Bone Neoplasms / Q000235:genetics* / Q000378:metabolism; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D006801:Humans; D051666:Kv1.5 Potassium Channel / Q000235:genetics* / Q000378:metabolism; D012516:Osteosarcoma / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D051666:Kv1.5 Potassium Channel; D034741:RNA, Small Interfering
keywords: Kv1.5 potassium channel; apoptosis; cell cycle; cell proliferation; osteosarcoma; signaling pathway