ABSTRACT
Bladder cancer (BCa) is one of the most prevalent cancers of the urinary system worldwide. Accumulating evidence suggests that long noncoding RNAs (lncRNAs) perform a vital function in the pathogenesis and progression of BCa. In the current study, we identified a novel lncRNA OXCT1-AS1 and investigated its role and potential mechanisms in BCa. The microarray results showed the expression of lncRNAs, microRNAs, and messenger RNAs between BCa primary tumor tissues and metastatic lymph nodes were significantly different. The quantitative polymerase chain reaction verification was performed to ensure the reliability of the screening results. The Cell Counting Kit 8 and transwell assay were used to assess the tumor cell proliferation and invasion abilities in vitro, respectively. The dual-luciferase activity assay was performed to investigate the potential mechanism of competing endogenous RNA network. lncRNA OXCT1-AS1, which elevated in metastasis lymph node, was significantly upregulated in BCa cell lines compared with SVHUC-1. We demonstrated OXCT1-AS1 inhibited miR-455-5p to decrease its binding to the JAK1 3'-untranslated region, which could upregulate the expression of JAK1 at the protein level, thus promoting BCa proliferation and invasion. Therefore, lncRNA OXCT1-AS1 could act as a potential biomarker and therapeutic target for patients with BCa.
Subject(s)
Gene Expression Regulation, Neoplastic/genetics , Janus Kinase 1/metabolism , MicroRNAs/metabolism , RNA, Long Noncoding/metabolism , Urinary Bladder Neoplasms/pathology , Cell Proliferation/genetics , Gene Expression Profiling , Humans , Janus Kinase 1/genetics , MicroRNAs/genetics , Oligonucleotide Array Sequence Analysis , RNA, Long Noncoding/genetics , Signal Transduction/physiology , Urinary Bladder Neoplasms/geneticsABSTRACT
BACKGROUND: Recent clinical trials indicated that metformin intake might play a protective role in the incidence and oncologic outcomes of various cancers. However, its protective effect on bladder cancer remains uncertain. METHODS: We performed a meta-analysis to investigate the association between metformin intake and bladder cancer risk as well as oncologic outcomes in diabetes mellitus (DM) patients. A comprehensive literature search was performed using PubMed, Embase, and the Cochrane Central Search Library in December 2017. Hazard ratio (HR) with 95% confidence interval (CI) was pooled. RESULTS: A total of 9 retrospective cohort studies with 1,270,179 patients were included. A meta-analysis revealed that metformin intake was associated with an increased recurrence-free survival (HRâ=â0.55, 95% confidence interval [CI]â=â0.35-0.88; Pâ=â.01; Iâ=â64%), improved progression-free survival (HRâ=â0.70, 95% CIâ=â0.51-0.96; Pâ=â.03; Iâ=â33%), and prolonged cancer-specific survival (HRâ=â0.57, 95% CIâ=â0.40-0.81; Pâ=â.002; Iâ=â0%). However, results demonstrated that metformin intake was not associated with a decreased incidence of bladder cancer (HRâ=â0.82, 95% CIâ=â0.61-1.09; Pâ=â.17; Iâ=â85%) or an increased overall survival in bladder cancer patients (HRâ=â0.83, 95% CIâ=â0.47-1.44; Pâ=â.50; Iâ=â64%). CONCLUSION: The present meta-analysis indicated that metformin intake could improve the prognosis of bladder cancer patients. Further prospective cohort studies and mechanistic studies are still required to determine the precise role of metformin in the initiation and progression of bladder cancer.
