title: Long noncoding RNA GAS5 inhibits malignant proliferation and chemotherapy resistance to doxorubicin in bladder transitional cell carcinoma.
abstract: OBJECTIVE
  Bladder cancer is the most general malignant cancer in genitourinary system, more than 90% of BCs are bladder transitional cell carcinomas (BTCC). This study aimed to investigate the clinical significance of growth arrest-specific 5 (GAS5) gene and its regulatory effects of malignant proliferation and chemotherapy resistance to doxorubicin in BTCC cells.
  
  
  METHODS
  The expression of GAS5 was detected by quantitative real-time PCR. Statistical analysis was used to determine the relationship between GAS5 expression and clinical features and the prognostic value of GAS5 for disease free survival. MTT assay was used to detect cell proliferation ability and chemosensitivity. Dual-color flow cytometric method was used to detect cell apoptosis. The expression of Bcl-2 protein was examined by western blot.
  
  
  RESULTS
  In this study, we found that GAS5 low-expressed in BTCC tissues and cells, and its low expression level had positive correlation with higher pathological grades of BTCC. Moreover, GAS5 was a prognostic biomarker of disease free survival for BTCC patients. GAS5 over-expression could inhibit cell proliferation of BTCC J82 and T24 cells significantly. The IC50 to doxorubicin in T24/DOX cells (resistance to doxorubicin) presented a conspicuous depression, GAS5 enhancement reduced the chemotherapy resistance to doxorubicin. GAS5 over-expression promoted apoptosis induced by doxorubicin in T24/DOX cells, and depressed the expression of anti-apoptosis protein Bcl-2. The results indicated that GAS5 regulated the chemotherapy resistance to doxorubicin via Bcl2 partly.
  
  
  CONCLUSIONS
  In summary, lncRNA GAS5 was a prognostic biomarker of disease free survival in BTCC patients, and acted as a tumor-suppressing gene to inhibit malignant proliferation and resistance to doxorubicin in BTCC cells. LncRNA GAS5 might be a novel potential therapeutic target for BTCC.
authors.affiliation: Department of Urinary Surgery, Shengjing Hospital, China Medical University, Shenyang, 110004, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Central Laboratory, School of Stomatology, China Medical University, Shenyang, 110007, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Urinary Surgery, Shengjing Hospital, China Medical University, Shenyang, 110004, China.
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Neurobiology, College of Basic Medicine, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, 110122, China. shangchao.net@163.com.
authors.forename: Chao
authors.initials: C
authors.lastname: Shang
mesh_terms: D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D017209:Apoptosis; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D005260:Female; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D062085:RNA, Long Noncoding / Q000502:physiology*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology
chemical_list: D000903:Antibiotics, Antineoplastic; C561567:GAS5 long non-coding RNA, human; D019253:Proto-Oncogene Proteins c-bcl-2; D062085:RNA, Long Noncoding; D004317:Doxorubicin
keywords: Bladder transitional cell carcinoma; Chemotherapy; Doxorubicin; GAS5; Long noncoding RNA