title: MicroRNA-294 Promotes Cellular Proliferation and Motility through the PI3K/AKT and JAK/STAT Pathways by Upregulation of NRAS in Bladder Cancer.
abstract: In our study we examined the role of microRNA-294 (miR-294) in bladder cancer and related mechanisms. Real-time polymerase chain reaction (RT-PCR) was performed to determine the expression level of miR-294. Western blot was used to determine the expression of NRAS, mainly factors in the PI3K/AKT and JAK/STAT pathways. Cell counting kit-8 assay, clonogenic assay, wound-healing assay, transwell and flow cytometry were used to explore, respectively, cell proliferation, survival, migration, invasion, and apoptosis of bladder cancer cell line T24. The expressions of miR-294 in bladder cancer cells including J82, HT1376, T24, and SW780 were significantly increased compared to those in human bladder epithelium cells (both HCV29 and SV-HUC-1). The proliferation rate, surviving fraction, migration, and invasion of T24 cells in miR-294 mimetic transfected group were significantly increased, while they were significantly decreased by miR-294 inhibitor transfection. Moreover, miR-294 suppression could increase the apoptotic rate of T24 cells. In addition, drug resistance of T24 cells to cisplatin was increased in miR-294 mimetic-treated group, while it was decreased by miR-294 inhibitor compared to empty control. Overexpression of miR-294 could upregulate NRAS expression in T24 cells and activate PI3K/AKT and JAK/STAT pathways. We found that miR-294 expression was positively related with proliferation and motility of T24 cells. Moreover, miR-294 suppression could promote the sensitivity of T24 cells to cisplatin. We also found miR-294 could upregulate NRAS and activate the PI3K/AKT and JAK/STAT pathways in T24 cells.
authors.affiliation: Department of Urology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, 264000, China. jtwu1006@163.com.
authors.forename: Yongwei
authors.initials: Y
authors.lastname: Li
authors.forename: Zhengfei
authors.initials: Z
authors.lastname: Shan
authors.forename: Chu
authors.initials: C
authors.lastname: Liu
authors.forename: Diandong
authors.initials: D
authors.lastname: Yang
authors.forename: Jitao
authors.initials: J
authors.lastname: Wu
authors.forename: Changping
authors.initials: C
authors.lastname: Men
authors.forename: Yankai
authors.initials: Y
authors.lastname: Xu
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics*; D020558:GTP Phosphohydrolases / Q000502:physiology*; D006801:Humans; D053612:Janus Kinases / Q000378:metabolism*; D008565:Membrane Proteins / Q000502:physiology*; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D050791:STAT Transcription Factors / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology*; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D008565:Membrane Proteins; D035683:MicroRNAs; D050791:STAT Transcription Factors; C000619554:microRNA-294 microRNA, human; D019869:Phosphatidylinositol 3-Kinases; D053612:Janus Kinases; D051057:Proto-Oncogene Proteins c-akt; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human