RESUMO
Bladder cancer (BC) is the most common malignant tumor in the urinary system, and its early diagnosis is conducive to improving clinical prognosis and prolonging overall survival time. However, few biomarkers with high sensitivity and specificity are used as diagnostic markers for BC. Multiple long non-coding RNAs (lncRNAs) are abnormally expressed in BC, and play key roles in tumorigenesis, progression and prognosis of BC. In this review, we summarize the expression, function, molecular mechanisms and the clinical significance of lncRNAs on bladder cancer. There are more than 100 dysregulated lncRNAs in BC, which are involved in the regulation of proliferation, cell cycle, apoptosis, migration, invasion, metabolism and drug resistance of BC. Meanwhile, the molecular mechanisms of lncRNAs in BC was explored, including lncRNAs interacting with DNA, RNA and proteins. Additionally, the abnormal expression of thirty-six lncRNAs is closely associated with multiple clinical characteristics of BC, including tumor size, metastasis, invasion, and drug sensitivity or resistance of BC. Furthermore, we summarize some potential diagnostic and prognostic biomarkers of lncRNA for BC. This review provides promising novel biomarkers in early diagnosis, prognosis and monitoring of BC based on lncRNAs.
RESUMO
BACKGROUND/AIMS: This study aims to identify whether Urothelial Cancer Associated 1 (UCA1) regulates mitochondrial metabolic reprogramming in bladder cancer, and to explore how UCA1 participates in mitochondrial metabolism by the UCA1/miR-195/ARL2 signaling pathway; these findings may be aid in the development of tumor diagnostic and therapeutic strategies. METHODS: Bladder tissues were obtained from patients. Stable cell lines were constructed, with ectopic expression of UCA1 in UMUC2 cells and knockdown of UCA1 in 5637 cells. The expression levels of UCA1, miR-195, and ARL2 were detected by real-time PCR, western blotting, and immunohistochemistry Cell viability was detected by Cell Counting Kit-8 (CCK8) assay; mitochondrial DNA copy numbers were tested by realtime PCR; ATP level was evaluated by ATP assay kit; mitochondrial membrane potential was analyzed by 5,5',6,6'-tetrachloro-1,1',3,3'- tetraethylbenzimidazolylcarbocyanine iodide (JC-1) fluorescent probe. miRNAs between UCA1 and ARL2 were predicted by TargetScan and RNAHybrid, and then determined by real-time PCR. Dual-luciferase activity assay and RNA immunoprecipitation (RIP) assay were used to verify the relationship between UCA1 and miR-195. The expression level of ARL2 was silenced by small interfering RNA(siRNA). For in vivo experiments, UCA1-silencing 5637 cells were subcutaneously injected into BALB/C nude mice to evaluate the effects of UCA1 on tumor progression by the regulation of miR-195 and ARL2. RESULTS: We demonstrate here that UCA1 enhances mitochondrial function in bladder cancer cells. UCA1 contributes to ARL2-induced mitochondrial activity, which plays an important role in mitochondrial function. UCA1, as a competing endogenous RNA (ceRNA), regulates mitochondrial function through upregulating ARL2. In this way, it inhibited the miR-195 signaling pathway to enhance mitochondrial function in bladder cancer. Additionally, ARL2 is a direct target of miR-195 and can be repressed by either miR-195 overexpression or UCA1 inhibition. Knockdown of ARL2 was analogous to the inhibition of UCA1 and the upregulation of miR-195. Animal experiments further indicated that UCA1 promoted bladder tumor growth by regulating miR-195 /ARL2. CONCLUSION: These data suggest that UCA1 enhanced mitochondrial function and cell viability through the UCA1/miR-195/ARL2 axis in vitro and in vivo. The elucidation of this signaling network provides a more adequate theoretical basis for understanding the molecular pathology of bladder cancer, and also UCA1 as a potential diagnosis and treatment target for bladder cancer.
