title: Long non-coding RNA LOC572558 inhibits bladder cancer cell proliferation and tumor growth by regulating the AKT-MDM2-p53 signaling axis.
abstract: Long non-coding RNAs (lncRNAs) have been suggested to play important roles in the progression of many cancers such as bladder cancer. However, the detailed mechanism has not been fully understood. We have previously identified a collection of aberrantly expressed lncRNAs in bladder cancer using microarray gene profiling assay. In the current study, we aim to further explore the expression profile and the function of LOC572558, one of the most deregulated lncRNAs in bladder cancer. A large cohort of human bladder cancer tissue samples with benign controls, as well as established human bladder cancer cell lines, has been examined for the expression of LOC572558. The biological functions of LOC572558 were examined by CCK-8 assay, flow cytometry analysis, and wound healing and transwell assays. Using a high-throughput phospho-proteome array, we identified proteins that were ectopic phosphorylated in bladder cancer cells where LOC572558 expression was upregulated. We demonstrated that LOC572558 expression was markedly decreased in bladder cancer tissues and bladder cancer cell lines. Moreover, ectopic expression of LOC572558 inhibited cell proliferation and motility, induced S phase arrest of the cell cycle and promoted cell apoptosis in T24 and 5637 bladder cancer cell lines. We further verified that overexpression of LOC572558 was associated with dephosphorylation of AKT, MDM2 and phosphorylation of p53 protein. Our data clearly demonstrated that LOC572558 is a tumor suppressor and regulates the p53 signaling pathway in bladder cancer. Thus, it may serve as a promising new diagnostic marker and therapeutic target in bladder cancer.
authors.affiliation: Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Dai
authors.affiliation: Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Hailiang
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Guohai
authors.initials: G
authors.lastname: Shi
authors.affiliation: Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Yijun
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. Electronic address: Dwye_fudan@126.com.
authors.forename: Dingwei
authors.initials: D
authors.lastname: Ye
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D057166:High-Throughput Screening Assays; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D040901:Proteomics / Q000379:methods; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism*; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D062085:RNA, Long Noncoding; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D051057:Proto-Oncogene Proteins c-akt
keywords: Bladder cancer; Long noncoding RNA; p53