title: RSK4 knockdown promotes proliferation, migration and metastasis of human breast adenocarcinoma cells.
abstract: RSK4 has been shown to inhibit the growth of certain cancer cells. The aim of this study was to construct a lentiviral vector of RSK4-shRNA (Lenti-RSK4-shRNA) to specifically block the expression of RSK4 in the human breast adenocarcinoma cell line MCF-7, and investigate the effect of the RSK4 gene on cell proliferation and invasion in vitro and in vivo. Lenti-RSK4-shRNA was stably transfected into MCF-7 cells. RSK4 mRNA and protein expression were measured by fluorescence quantitative RT-PCR and western blot analysis. Cell proliferation was evaluated by MTT assays and flow cytometric analysis. Invasion was evaluated by Transwell assays and xenograft nude mouse models. The expression of RSK4 mRNA, Ki-67 mRNA, cyclin D1 mRNA, CXCR4 mRNA and E-cadherin mRNA of tumor xenografts were detected by fluorescence quantitative RT-PCR. Significant decreases in RSK4 mRNA and protein expression was detected in MCF-7 cells carrying lentiviral RSK4-shRNA vector. The cell proliferation was significantly promoted in the RSK4-shRNA group as compared to that in the negative and blank control group. In addition, the number of cells in the S phase in the RSK4‑shRNA group was significantly greater than the blank and negative control groups (P<0.05). Furthermore, the number of invading cells was increased in the RSK4-shRNA (P<0.05). In vivo, we also found that the knockdown of RSK4 promoted tumorigenicity and migration in the xenograft nude mouse model. In addition, we showed that the RSK4 mRNA and E-cadherin mRNA expression were significantly lower in the RSK4-shRNA group compared to that in negative and blank control group (both P<0.05), while the Ki-67 mRNA, cyclin D1 mRNA and CXCR4 mRNA were higher in the shRNA group compared to that in negative and blank control group (both P<0.05). In conclusion, downregulation of RSK4 expression is indicated to be associated with tumor cell proliferation and invasion, and silencing of the RSK4 may be involved in the development and progression of breast cancer through the changes of Ki-67, cyclin D1, CXCR4 and E-cadherin, and suggesting that RSK4 may act as a potential cancer suppressor gene and therapeutic target for the treatment of breast cancer.
authors.affiliation: Department of Breast Surgery, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Jia
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Breast Surgery, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Qiu-Yun
authors.initials: QY
authors.lastname: Li
authors.affiliation: Department of Breast Surgery, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Jian-Lun
authors.initials: JL
authors.lastname: Liu
authors.affiliation: Department of Breast Surgery, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.affiliation: Department of Breast Surgery, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Hua-Wei
authors.initials: HW
authors.lastname: Yang
authors.affiliation: Department of Breast Surgery, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Tang
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000096:biosynthesis; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000037:antagonists & inhibitors / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
chemical_list: D009363:Neoplasm Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C501305:RPS6KA6 protein, human; D038744:Ribosomal Protein S6 Kinases, 90-kDa