Original ArticlesLong non-coding RNA LOC572558 inhibits bladder cancer cell proliferation and tumor growth by regulating the AKT–MDM2–p53 signaling axis
Introduction
Bladder cancer is one of the most common urological malignancies world-wide and the overall survival rate remains poor in invasive diseases [1]. The advances in finding suitable therapies to increase survival rates were limited because the pathophysiological mechanisms causing bladder cancer are still unknown. Thus, a detailed understanding of the mechanisms underlying bladder cancer development and progression is essential for improving diagnosis, prevention and treatment of this disease.
The sequencing of the human genome led to the astonishing discovery that >90% of our genome is transcribed to a versatile group of RNA transcripts without protein coding potential [2]. Recently, thousands of long non-coding RNAs (lncRNAs) have been identified and accumulating evidence demonstrates that lncRNAs function as versatile regulators at each step during genetic information processing in the living cell [3]. Functional studies have indicated that some lncRNAs such as PlncRNA-1, HOTAIR and LSINCT5 are involved in human cancer pathogenesis, acting as either oncogenes or tumor suppressors [4], [5], [6], [7]. Recently, several lncRNAs which interact with major cellular pathways controlling proliferation, differentiation, or apoptosis, and alterations in their function are found to be involved in the pathogenesis of bladder cancer, including UCA1, ncRAN, GAS5, GHET1 and MALAT1 [8], [9], [10], [11], [12]. We previously identified a collection of aberrantly expressed lncRNAs in bladder cancer by microarray and LOC572558 was validated to be one of the most downregulated lncRNAs for the first time, indicating that LOC572558 might participate in the carcinogenesis and progression of bladder cancer [13]. However, the potential molecular mechanism of lncRNAs in the development of bladder cancer has not been well examined. Thus, in the present study we aimed to explore the expression level and the functional role of LOC572558 in bladder cancer. Our results might help identify a new therapeutic target and diagnostic marker for bladder cancer.
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Tissue samples and cell lines
Human bladder cancer cells T24 and 5637 were obtained from the American Type Culture Collection (ATCC, Manassas, VA) and maintained in RPMI 1640 plus 10% fetal bovine serum (FBS) (GIBCO, Carlsbad, CA), in a humidified incubator with a 5% CO2 atmosphere at 37 °C. The human bladder epithelial cell line HUM-CELL-0046 was obtained from PriCells (Wuhan, China) and maintained in MED-0001 (PriCells, Wuhan, China). Human bladder tissues that were surgically resected were obtained from the tissue bank
LOC572558 level was downregulated in bladder cancer
To determine the role of LOC572558 in bladder cancer progression, we first examined its expression levels in bladder cancer cells and bladder cancer tissues using quantitative real-time PCR. We assessed LOC572558 expression in human bladder cancer tissues. The LOC572558 level was downregulated in 79% of bladder cancer tissues compared with adjacent normal tissues (Fig. 1A). We next verified that expression of LOC572558 was decreased in two bladder cancer cell lines relative to the expression in
Discussion
LncRNAs are RNA transcripts of more than 200 nucleotides with no protein encoding functions [15]. An increasing number of studies indicate that the molecular mechanisms of carcinogenesis are relevant not only to protein coding genes but also to non-coding regulatory RNAs [15]. LncRNAs emerged rapidly as a diverse group of essential regulators of genetic information flow that interact with the epigenetic, transcriptional, and posttranscriptional pathways of cell proliferation, differentiation,
Conflict of interest
The authors declare no conflict of interest.
Acknowledgements
This study was supported by the National Natural Science Foundation of China (No. 81302216) and the Specialized Research Fund for the Doctoral Program of Higher Education of China (No. 20130071110056).
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