ABSTRACT
The incidence and mortality rate of bladder cancer have dramatically expanded, so it's urgent to discover new biomarker and therapeutic target for bladder cancer. Recently, lncRNA has been identified as oncogene or tumor suppressor to regulate the tumorigenesis. LncRNA ZFAS1 has been confirmed as oncogene in various tumors. However, the expression, function, and underlying mechanism of ZFAS1 in bladder carcinogenesis have yet to be totally clarified. In the current study, our data demonstrated that ZFAS1 expression was significantly upregulated in bladder cancer tissues and cell lines. Furthermore, Kaplan-Meier analysis revealed that high ZFAS1 expression was significantly associated with unfavorable progression free survival (PFS) (Pâ¯=â¯0.0034â¯<â¯0.01) and overall survival (OS) (Pâ¯=â¯0.0041â¯<â¯0.01) of bladder cancer patients. Moreover, silencing of ZFAS1 expression could markedly suppress bladder cancer cells proliferation and colony formation, arrest cell cycle, promote cell apoptosis and inhibit cell migration in vitro. In addition, bioinformatics analysis, luciferase reporter assay, and pull down assay revealed that ZFAS1 straightly interacted with miR-329. Lastly, rescue experiments confirmed that miR-329 inhibitor reversed the tumor suppressing roles of ZFAS1 knockdown on bladder cancer cells. Collectively, our results illuminated that ZFAS1 could serve as an oncogene in the tumorigenesis of bladder cancer, and discovered the functional regulatory network of ZFAS1 sponging miR-329.
Subject(s)
Carcinogenesis/genetics , Carcinogenesis/pathology , MicroRNAs/metabolism , RNA, Long Noncoding/metabolism , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/pathology , Apoptosis/genetics , Base Sequence , Cell Cycle/genetics , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Cell Survival/genetics , Gene Expression Regulation, Neoplastic , Gene Knockdown Techniques , Humans , MicroRNAs/genetics , Neoplasm Invasiveness , Prognosis , RNA, Long Noncoding/genetics , Tumor Stem Cell Assay , Up-Regulation/geneticsABSTRACT
Renal cell carcinoma (RCC) is the most common primary malignancy of the kidney and one of the most lethal genitourinary malignancies. Clear-cell renal cell carcinoma (ccRCC) has an extremely poor prognosis because of a high potential for tumor growth, vascular invasion, metastasis and recurrence. Unfortunately, the mechanism of RCC growth and metastasis is not well understood. In this report, we for the first time demonstrated ubiquitin protein ligase E3C (UBE3C) as a driving factor for RCC growth and metastasis. UBE3C expression was increased in ccRCC tissues compared with adjacent normal tissues. ccRCC patients with high UBE3C protein expression in tumors were associated with significantly worse postoperative survival. Knockdown of UBE3C expression in ACHN cells inhibited cell proliferation, migrations and invasiveness in vitro while overexpression of UBE3C in 786-O cells exerted the opposite effects. UBE3C up-regulated ß-catenin protein levels and promoted ß-catenin nuclear accumulation, leading to the activation of the Wnt/ß-catenin signal pathway in RCC cells. Collectively, these observations suggest that UBE3C plays an important role in RCC development and progression, and UBE3C may be a novel target for prevention and treatment of ccRCC.
