title: miR-101 suppresses vascular endothelial growth factor C that inhibits migration and invasion and enhances cisplatin chemosensitivity of bladder cancer cells.
abstract: BACKGROUND
  The microRNA miR-101 is downregulated in several cancers, including bladder cancer. However, miR-101's role in the invasion, metastasis, and chemosensitivity of bladder cancer cells remains unclear. This study was conducted to determine miR-101's role on the lymphangiogenic molecule vascular endothelial growth factor C (VEGF-C) and their effects upon bladder cancer cell migration, invasion, and chemosensitivity to cisplatin.
  
  
  METHODS
  Two bladder cancer cell lines (T24 and 5637) and the tool cell line 293T were employed here. Bladder cancer cells were transfected with either a miR-101 overexpression vector or a scrambled-sequence lentivirus, both of which exhibited a high transfection efficiency. Non-transfection was used as a mock negative control. Wound healing and Transwell assays were performed to measure cell migration and invasiveness. A luciferase reporter assay was performed to validate miR-101's interaction with VEGF-C's 3' untranslated region followed by RT-PCR and Western blot confirmation. An MTS assay was used to evaluate the cisplatin sensitivity of the cell lines.
  
  
  RESULTS
  miR-101 overexpression significantly inhibited the migration and invasiveness while significantly enhancing cisplatin sensitivity. miR-101 negatively regulated VEGF-C protein expression, and VEGF-C overexpression rescued the effects of miR-101 overexpression, indicating that miR-101 negatively regulates VEGF-C protein expression post-transcriptionally. miR-101 and VEGF-C interference independently enhanced cisplatin cytotoxicity in bladder cancer cells.
  
  
  CONCLUSIONS
  miR-101 suppresses VEGF-C expression, inhibits cell migration and invasion, and increases cisplatin sensitivity in bladder cancer cells. This study provides new insight into miR-101's role in bladder cancer and shows miR-101's promise as a potential molecular target for bladder cancer.
authors: Department of Urology, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Changsha, Hunan, 410008, China.
authors: Ye
authors: Y
authors: Lei
authors: Department of Biochemistry and Molecular Biology, College of Basic Medicine, Key Laboratory of Medical Biotechnology of Hebei Province, Hebei Medical University, No. 361 Zhongshan East Road, Shijiazhuang, Hebei, 050017, China.
authors: Bin
authors: B
authors: Li
authors: Department of Urology, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Changsha, Hunan, 410008, China.
authors: Shiyu
authors: S
authors: Tong
authors: Department of Urology, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Changsha, Hunan, 410008, China.
authors: Lin
authors: L
authors: Qi
authors: Department of Urology, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Changsha, Hunan, 410008, China.
authors: Xiheng
authors: X
authors: Hu
authors: School of Life Sciences, Central South University, No. 110 Xiangya Road, Changsha, Hunan, 410008, China.
authors: Yunbo
authors: Y
authors: Cui
authors: Department of General Surgery, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Changsha, Hunan, 410008, China.
authors: Zengbo
authors: Z
authors: Li
authors: Department of Urology, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Changsha, Hunan, 410008, China.
authors: Wei
authors: W
authors: He
authors: Department of Urology, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Changsha, Hunan, 410008, China.
authors: Xiongbing
authors: X
authors: Zu
authors: Department of Urology, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Changsha, Hunan, 410008, China.
authors: Zhi
authors: Z
authors: Wang
authors: Department of Urology, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Changsha, Hunan, 410008, China.
authors: Minfeng
authors: M
authors: Chen
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000970:Antineoplastic Agents / Q000494:pharmacology; D001483:Base Sequence; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002945:Cisplatin / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D009154:Mutation; D009361:Neoplasm Invasiveness; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D042582:Vascular Endothelial Growth Factor C / Q000235:genetics* / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D000970:Antineoplastic Agents; C534072:MIRN101 microRNA, human; D035683:MicroRNAs; D042582:Vascular Endothelial Growth Factor C; D008156:Luciferases; D002945:Cisplatin