Search

Objective Long noncoding RNAs (lncRNAs) offer great potential as cancer biomarkers. This study was performed to assess the applicability of serum lncRNA urothelial carcinoma-associated 1 (UCA1) as a diagnostic and/or prognostic biomarker for hepatocellular carcinoma (HCC). Methods We examined UCA1 expression in serum samples from 105 patients with HCC, 105 patients with benign liver disease (BLD), and 105 healthy volunteers using reverse-transcription polymerase chain reaction and analyzed the relationship between serum UCA1 and clinicopathological parameters of HCC as well as survival. Results Expression of serum UCA1 was significantly higher in patients with HCC and allowed for discrimination of HCC from BLD and healthy controls. High expression of serum UCA1 was significantly associated with a high tumor grade, large tumor size, positive vascular invasion, and advanced TNM stage. Multivariate analysis revealed that a high serum UCA1 level was an independent unfavorable prognostic factor for HCC. Conclusions Our results confirm the upregulation of serum UCA1 expression in HCC and indicate its clinical value as a noninvasive biomarker for HCC screening and prognostic prediction.

Long non-coding RNAs (lncRNAs) have been documented to play key roles in a wide range of pathophysiological processes, including cancer initiation and progression. Recently, the aberrant expression of urothelial carcinoma associated 1 (UCA1) was observed in many types of cancers. However, its clinical relevance and exact effects in cholangiocarcinoma (CCA) remains unknown. In the present study, we aimed to investigate the clinical significance of UCA1 and evaluate its prognostic value in patients with CCA. Besides, the functional roles of UCA1 were detected both in vitro and in vivo . Moreover, potential signaling pathways were explored to clarify the molecular mechanisms underlying CCA cell proliferation. The results indicated that UCA1 transcription is enhanced in both CCA tissue samples and cell lines, and this overexpression is associated with tumor stage ( P = 0.007), lymph node invasion ( P = 0.027), TNM stage ( P = 0.004) and postoperative recurrence ( P = 0.033) of CCA patients. Besides, UCA1 could function as an independent prognostic predictor for overall survival in patients with CCA ( P = 0.014). For the part of functional assays, knockdown of UCA1 could attenuate CCA cell growth both in vitro and in vivo . Besides, UCA1 facilitates apoptosis via Bcl-2/caspase-3 pathway. In addition, UCA1 regulates migration and invasion potential of CCA cells by affecting EMT. Furthermore, AKT/GSK-3β axis was activated to upregulate CCND1 expression due to overexpression of UCA1 in CCA. To summary, UCA1 might be a potentially useful prognostic biomarker and therapeutic target for CCA., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.

Neural stem cells are able to self-renew and generate glial and neuronal lineages. Neural stem cell may serve as therapeutic method for neurological disorders including spinal cord injuries, Parkinson's disease, Huntington's disease and Alzheimer's disease. Long noncoding RNAs (lncRNAs) are longer than 200 nucleotides with limited protein-coding capacity. Recent studies have demonstreated that lncRNAs play an important role in several cellular processes including cell differentiation, cell development, proliferation, apoptosis, invasion and migration. However, the role of lncRNA human urothelial carcinoma associated 1 (UCA1) in the development of neural stem cells remains unknown. In this study, we showed that the expression of UCA1 was upregulated in the neural stem cell in a time-dependent manner. Knockdown of UCA1 suppressed the neural stem cell proliferation. Inhibition of UCA1 decreased the expression of nestin and the formation of neurosphere. Moreover, knockdown of UCA1 suppressed the neural stem cell differentiation to astrocyte and promoted the neural stem cell differentiation to neuron. Furthermore, we demonstrated that knockdown of UCA1 increased the expression of miR-1 in the neural stem cell and suppressed the expresion of Hes1, which is one target gene of miR-1. In addition, ectopic expression of Hes1 could impair siUCA1-induced neural stem cells proliferation. Overexpression of Hes1 suppressed siUCA1-induced β-tubulin expression and promoted siUCA1-inhibited GFAP expression in the neural stem cell. These results suggested that UCA1 regulated the neural stem cell proliferation and differentiation through regulating Hes1 expression., Competing Interests: None.

Osteoarthritis (OA) is a common degenerative disease characterized by degeneration of articular cartilage. Increasing studies showed that long noncoding RNAs (lncRNAs) play important roles in the cartilage damage. However, little is known about the role of UCA1 in the osteoarthritis. The expression level of UCA1 was upregulated in the OA cartilage. Overexpression of UCA1 suppressed the miR-204-5p expression in the chondrocytes. The expression of miR-204-5p was downregulated in the OA cartilage. Moreover, the expression of miR-204-5p was negatively correlated with the UCA1 expression in the OA cartilage. Elevated expression of UCA1 promoted the chondrocytes cell proliferation and overexpression of miR-204-5p suppressed chondrocytes cell proliferation. In addition, overexpression of UCA1 decreased the expression of the type II collagen and type IV collagen expression in the chondrocytes. Elevated expression of miR-204-5p promoted the type II collagen and type IV collagen expression in the chondrocytes. We idetified MMP-13 was a direct target gene of miR-204-5p in the chondrocytes. Overexpression of UCA1 enhanced the MMP-13 expression in the chondrocytes. Elevated expression of UCA1 regulated the chondrocytes cell proliferation and collagen expression through inhibiting the miR-204-5p expression.These results suggested that UCA1 played as an important regulator of survival and matrix synthesis of chondrocytes partly through suppressing the miR-204-5p expression., Competing Interests: CONFLICTS OF INTEREST None.

The long non-coding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) has been recently shown to be dysregulated during disease occurrence and to play an important role in the progression of several cancers. However, the biological role and potential regulation mechanism of UCA1 in the carcinogenesis of gastric cancer remain unclear. In the present study, we found that UCA1 was aberrantly upregulated in gastric cancer tissues and gastric cancer cell lines, and was associated with TNM stage and metastasis. UCA1 silencing significantly inhibited gastric cancer BGC-823 cell proliferation and increased its apoptosis. We also found that UCA1 played an important role in the migration and invasion of gastric cancer cells in vitro and in vivo . The molecular mechanism of UCA1 suggested that UCA1 regulates the PI3K-Akt-mTOR signaling proteins and their downstream mediators, to alter gastric cancer progression in vitro and in vivo . Collectively, the results showed a pivotal role of UCA1 in the tumorigenesis of gastric cancer. In addition, the study characterized a novel lncRNA-mRNA regulatory network, which may lead to a better understanding of the pathogenesis of gastric cancer and assist in lncRNA-directed diagnosis and therapy for this malignancy., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.

Aim: To identify sets of functionally related long noncoding RNAs (lncRNAs) and mRNAs and to evaluate the importance of lncRNAs in an lncRNA-mRNA network., Methods: We carried out weighted gene co-expression network analysis and enrichment analyses to identify functional modules of co-expressed lncRNAs and mRNAs in human peripheral blood mononuclear cells of 43 females., Results: We identified seven modules and found hub lncRNAs in each module. Four of the seven modules had significant gene ontology enrichments. Some of the hub lncRNAs (e.g., SSX8, UCA1, HOXA-AS2, STARD4-AS1 and PCBP1-AS1) have known functions related with diseases such as cancers., Conclusion: We identified seven biologically important lncRNA and mRNA integrative modules in females and showed that lncRNAs might play important roles in lncRNA-mRNA co-expression modules.

Background: Urothelial Carcinoma Associated 1 (UCA1) was an originally identified lncRNA in bladder cancer. Previous studies have reported that UCA1 played a significant role in various types of cancer. This study aimed to clarify the prognostic value of UCA1 in digestive system cancers., Results: The meta-analysis of 15 studies were included, comprising 1441 patients with digestive system cancers. The pooled results of 14 studies indicated that high expression of UCA1 was significantly associated with poorer OS in patients with digestive system cancers (HR: 1.89, 95 % CI: 1.52-2.26). In addition, UCA1 could be as an independent prognostic factor for predicting OS of patients (HR: 1.85, 95 % CI: 1.45-2.25). The pooled results of 3 studies indicated a significant association between UCA1 and DFS in patients with digestive system cancers (HR = 2.50; 95 % CI = 1.30-3.69). Statistical significance was also observed in subgroup meta-analysis. Furthermore, the clinicopathological values of UCA1 were discussed in esophageal cancer, colorectal cancer and pancreatic cancer., Materials and Methods: A comprehensive retrieval was performed to search studies evaluating the prognostic value of UCA1 in digestive system cancers. Many databases were involved, including PubMed, Web of Science, Embase and Chinese National Knowledge Infrastructure and Wanfang database. Quantitative meta-analysis was performed with standard statistical methods and the prognostic significance of UCA1 in digestive system cancers was qualified., Conclusions: Elevated level of UCA1 indicated the poor clinical outcome for patients with digestive system cancers. It may serve as a new biomarker related to prognosis in digestive system cancers.

The pivotal role of the long non-coding RNA (lncRNA) urothelial carcinoma associated 1 (UCA1) in anti-cancer drug resistance has been confirmed in many cancers. Overexpression of lncRNA UCA1 correlates with resistance to chemotherapeutics such as cisplatin, gemcitabine, 5-FU, tamoxifen, imatinib and EGFR-TKIs, whereas lncRNA UCA1 knockdown restores drug sensitivity. These studies highlight the potential of lncRNA UCA1 as a diagnostic and prognostic biomarker, and a therapeutic target in malignant tumors. In this review, we address the role of lncRNA UCA1 in anti-cancer drug resistance and discuss its potential in future clinical applications., Competing Interests: CONFLICTS OF INTEREST The authors declare no potential conflicts of interest.

Despite great scientific advances have been achieved in cancer treatment in recent years, the death rate of bladder cancer has been staying at a high level. Metformin, a widely-used and low-cost diabetes medicine, might have the potential of anticancer. The aim of this study was to evaluate the effects of metformin on bladder cancer cells and to identify potential molecular targets and signaling pathways. Bladder cancer 5637 cells transfected with either pcDNA/UCA1 vector or pcDNA3.1 empty vector were treated with various doses of metformin for different periods of time, and then cell proliferation and glycolysis were assessed. Reverse transcription polymerase chain reaction and Western blotting were applied to examine the expression of long non-coding RNA UCA1 and mammalian target of rapamycin-signal transducer and activator of transcription pathway molecules. We found metformin inhibited bladder cancer cell proliferation in a dose- and time-dependent manner. UCA1-overexpressed 5637 cells showed increased proliferation and glycolysis compared with control cells. Metformin downregulated both endogenous and exogenous UCA1 expression, leading to the inhibition of mammalian target of rapamycin-signal transducer and activator of transcription 3-hexokinase 2 signaling pathway. Our study provided the first evidence that metformin inhibited proliferation and glycolysis in cancer cells through regulation of long non-coding RNA UCA1. The discovery also suggested the important roles of long non-coding RNA in chemoprevention, which is a property of metformin.

Urine UCA1 has been reported as a potential novel diagnostic biomarker for bladder cancer in several studies, but their results are inconsistent. As a result of this, a diagnostic meta-analysis to assess the diagnostic performance of urine UCA1 in detecting bladder cancer was conducted. A systematic electronic and manual search was performed for relevant literatures through PubMed, Cochrane library, Chinese Wan Fang and the China National Knowledge Infrastructure (CNKI) databases up to December 30, 2016. The quality of the studies included in this meta-analysis was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. All analyses were conducted using stata12.0 software. Six studies collectively included 578 bladder cancer patients and 562 controls met the eligible criteria. The overall diagnostic accuracy was measured by the following: sensitivity 0.81 (95% CI = 0.75-0.86), specificity 0.86 (95% CI = 0.73-0.93), positive likelihood ratio 5.85 (95% CI = 2.72-12.57), negative likelihood 0.22 (95% CI = 0.15-0.32), diagnostic odds ratio 27.01 (95% CI = 8.69-83.97), and area under the curve 0.88 (95% CI = 0.85-0.91). Meta-regression analysis suggested that ethnicity significantly accounted for the heterogeneity of sensitivity. Deeks' funnel plot asymmetry test (P = 0.33) suggested no potential publication bias. According to our results, urine UCA1 has greater diagnostic value in diagnosing bladder cancer, however further research studies with more well-designed and large sample sizes are required to confirm our findings.

Numerous studies suggested that long non-coding RNA UCA1 was highly expressed and played critical roles in the development and progression of various cancerous tissues and cells. However, little is known about the association between UCA1 and tumor lymph node metastasis. In our study, a systematic review was conducted to evaluate the association between UCA1 expression and tumor lymph node metastasis and explore whether UCA1 can be a potential molecular marker for predicting the multiple tumor lymph node metastasis. The meta-analysis result showed that the number of lymph node metastasis in different tumorous types of UCA1 high-expression group was significantly higher compared with UCA1 low-expression group (pooled odds ratio = 2.13, 95% confidence interval: 1.60-2.84, p < 0.05). To verify whether the above result was still valid in specific tumor type, we conducted a meta-analysis including four articles on colorectal cancer (pooled odds ratio = 2.07, 95% confidence interval: 1.28-3.34, p < 0.05). Based on the existing results, it can be explained that the long non-coding RNA UCA1 was significantly associated with lymph node metastasis and both the results revealed that compared with UCA1 low-expression group, the lymph node metastasis rate of UCA1 high-expression group was statistically significantly elevated. Therefore, long non-coding RNA UCA1 has the potential of being a biological marker for predicting lymph node metastasis.

Background: Several long noncoding RNAs (lncRNAs) are involved in oncogenesis., Methods and Results: Our microarray analysis showed that numerous lncRNAs are dysregulated in hypopharyngeal squamous cell carcinoma (HSCC) tumor tissues as compared with normal tissues. Among those lncRNAs, urothelial carcinoma-associated 1 (UCA1) has been found to have an oncogenic role in HSCC. We confirmed the upregulation of UCA1 in HSCC by assessing its expression levels in a cohort of 53 patient tumors and paired non-tumor samples. In addition, we found that high UCA1 expression was significantly associated with advanced T category, late clinical stage, greater lymphatic invasion, and worse prognosis. Furthermore, in vitro experiments demonstrated that UCA1 functioned as an oncogene by promoting the proliferation and invasion and preventing the apoptosis of HSCC cells., Conclusions: Taken together, our findings for the first time identify the role of UCA1 as a tumor promoter and a pro-metastatic factor in HSCC, demonstrating that UCA1 is a potential prognostic biomarker and therapeutic target in HSCC.

Artesunate (ART) is a sesquiterpene lactone isolated from the leafy portions of the Chinese herb Artemisia annua. Here, we evaluated the effect of ART on the prostate cancer (PCa) cell lines DU145 and LNCaP and explored its potential mechanisms. ART inhibited the viability and mobility of DU145 and LNCaP cells. Mechanistically, we found that UCA1, one of the most important lncRNAs in malignancies of the urinary system, may be a potential mediator contributing to the tumor suppressor function of ART. First, the UCA1 level was reduced significantly after being exposed to ART. In addition, UCA1 was up-regulated in prostate cancer tissues compared to hyperplastic prostatic tissues, and a higher UCA1 level predicted poor prognosis in PCa patients. Furthermore, reintroduction of UCA1 into PCa cells reversed the effect of ART on apoptosis and metastatic ability. Then we determined that the miR-184/Bcl-2 axis might be the downstream signaling pathway of UCA1 upon ART treatment. UCA1 binds to miR-184 through its seed sequences and may function as a sponge for miR-184.

CRISPR/Cas9 is a novel and effective genome editing technique, but its application is not widely expanded to manipulate long non-coding RNA (lncRNA) expression. The lncRNA urothelial carcinoma-associated 1 (UCA1) is upregulated in bladder cancer and promotes the progression of bladder cancer. Here, we design gRNAs specific to UCA1 and construct CRISPR/Cas9 systems targeting UCA1. Single CRISPR/Cas9-UCA1 can effectively inhibit UCA1 expression when transfected into 5637 and T24 bladder cancer cells, while the combined transfection of the two most effective CRISPR/Cas9-UCA1s can generate more satisfied inhibitory effect. CRISPR/Cas9-UCA1s attenuate UCA1 expression via targeted genome-specific DNA cleavage, resulting in the significant inhibition of cell proliferation, migration and invasion in vitro and in vivo. The mechanisms associated with the inhibitory effect of CRISPR/Cas9-UCA1 on malignant phenotypes of bladder cancer are attributed to the induction of cell cycle arrest at G1 phase, a substantial increase of apoptosis, and an enhanced activity of MMPs. Additionally, urinary UCA1 can be used as a non-invasive diagnostic marker for bladder cancer as revealed by a meta-analysis. Collectively, our data suggest that CRISPR/Cas9 technique can be used to down-modulate lncRNA expression, and urinary UCA1 may be used as a non-invasive marker for diagnosis of bladder cancer.

Radioresistance remains a significant obstacle in the treatment of Prostate Cancer (PCa). To simulate the clinical scenario of irradiation resistance (IRR), we created DU145-IRR PCa cell lines by treatment with 2 Gy daily IR for 59 fractions. DU145-IRR cells acquired an aggressive phenotype as evidenced by increased clonogenic survival, tumorigenic potential and invasiveness. We performed transcriptome profiling to discover dysregulated genes in DU145-IRR cells and identified the long non-coding RNA (lncRNA), Urothelial carcinoma-associated 1 (UCA1). We first investigated the role of UCA1 in radiation response and found that UCA1 abundance was significantly higher in DU145-IRR cells compared to control cells. UCA1 siRNA-knockdown reversed the aggressive phenotype and significantly increased sensitivity to IR. UCA1 depletion inhibited growth, induced cell cycle arrest at the G2/M transition and decreased activation of the pro-survival Akt pathway. We then studied the clinical significance of UCA1 expression in two independent cohorts of PCa patients: MSKCC (130 patients) and CPC-GENE (209 patients). UCA1 over-expression was associated with decreased 5-year disease-free survival in MSKCC patients (HR = 2.9; p = 0.007) and a trend toward lower biochemical recurrence-free survival in CPC-GENE patients (HR = 2.7; p = 0.05). We showed for the first time that UCA1 depletion induces radiosensitivity, decreases proliferative capacity and disrupts cell cycle progression, which may occur through altered Akt signaling and induced cell cycle arrest at the G2/M transition. Our results indicate that UCA1 might have prognostic value in PCa and be a potential therapeutic target.

Although previous studies suggested that microRNA-506-3p (miR-506-3p) was frequently downregulated, and functioned as a tumor suppressor in several cancers, the biological role and intrinsic regulatory mechanisms of miR-506-3p in non-small cell lung cancer (NSCLC) remain elusive. The present study found miR-506-3p expression was downregulated in advanced NSCLC tissues and cell lines. The expression of miR-506-3p in NSCLC was inversely correlated with larger tumor size, advanced TNM stage and lymph node metastasis. In addition, we also found patients with lower expression of miR-506-3p had a poor prognosis than those patients with higher expression of miR-506-3p. Function studies demonstrated that aberrant miR-506-3p expression modulates tumor cell growth, cell mobility, cell migration and invasion in vitro and in vivo. Mechanistic investigations manifested that coactosin-like protein 1 (COTL1) was a direct downstream target of miR-506-3p. Knockdown of COTL1 mimicked the tumor-suppressive effects of miR-506-3p overexpression in A549 cells, whereas COTL1 overexpression enhanced the tumorigenic function in HCC827 cells. Importantly, we also found GATA3 transcriptionally actives miR-506-3p expression, and the long non-coding RNA urothelial carcinoma-associated 1 (UCA1) exerts oncogenic function in NSCLC by competitively 'sponging' miRNA-506. Together, our combined results elucidated genetic and epigenetic silencing of miR-506-3p enhances COTL1 oncogene expression to foster NSCLC progression.

Accumulating evidences indicated that UCA1 expression was up-regulated in various cancers, and high UCA1 expression was correlated with metastasis and prognosis. This meta-analysis collected all eligible studies and explored the relationships between UCA1 expression and lymph node metastasis (LNM) or overall survival (OS). Literature collection was performed by using electronic databases PubMed, Cochrane Library, and Web of Science (up to June 13, 2016). According to the inclusion and exclusion criteria, twelve studies were included in the meta-analysis. The result showed that high UCA1 expression was correlated with more LNM (OR=2.50, 95 %CI: 1.58-3.96, p<0.0001) in a random-effects model (I2=45 %, p=0.08) and could predict poor OS in cancer patients, with pooled hazard ratio (HR) of 1.65 [95% confidence interval (CI) 1.44-1.88, p<0.00001] indicated by a fixed-effects model (I2=35%, p=0.11). In conclusion, the present meta-analysis demonstrated that high expression of UCA1 might serve as a common molecular marker for predicting lymph node metastasis and prognosis in various cancers.

Recent studies reported that long non-coding RNAs (lncRNAs) might play critical roles in regulating endocrine resistance of breast cancer. Urothelial carcinoma-associated 1 (UCA1) is an lncRNA with an oncogenic role in breast cancer. This study aimed to investigate whether UCA1 is involved in acquired tamoxifen resistance in estrogen receptor (ER)-positive cancer cells. Our findings reveal that tamoxifen induces UCA1 upregulation in ER-positive breast cancer cells in a HIF1α-dependent manner. UCA1 upregulation results in significantly enhanced tamoxifen resistance. The upregulated UCA1 sponges miR-18a, which is a negative regulator of HIF1α. Therefore, UCA1 upregulation is further enhanced through a miR-18a-HIF1α feedback loop. In addition, our data also showed that miR-18a is a modulator of tamoxifen sensitivity due to its regulative effect on cell cycle proteins. miR-18a inhibitor reduced the sensitivity of MCF-7 cells to tamoxifen, while miR-18a mimics sensitized BT474 cells to tamoxifen. Therefore, miR-18a downregulation also partly contributes to acquired tamoxifen resistance in the cancer cells. These findings provide some useful information for future clinical treatment of tamoxifen resistance.

Background: Numerous studies have shown that the expression of UCA1 was aberrantly upregulated in various cancer types. High expression of UCA1 was reported to be associated with unfavorable prognosis in cancer patients., Results: A total of 1240 patients from 15 articles were included. The results indicated that a significantly shorter OS was observed in patients with high expression level of UCA1 (HR = 1.71, 95% CI: 1.43-1.99), in the subgroup analysis, the association was also observed in patients with cancers of digestive system (HR = 2.12, 95% CI: 1.59-2.66). Statistical significance was also observed in subgroup meta-analysis stratified by the cancer type, cut-off value, analysis type and sample size. Furthermore, poorer DFS was observed in patients with high expression level of UCA1 (HR = 2.54; 95% CI: 1.09-4.00). Additionally, the pooled odds ratios (ORs) showed that increased UCA1 was also related to positive lymph node metastasis (OR = 2.98, 95% CI: 2.06-4.30), distant metastasis (OR = 3.14, 95% CI: 1.77-5.58) and poor clinical stage (OR = 2.76, 95% CI: 2.08-3.68)., Materials and Methods: A comprehensive retrieval was conducted in multiple databases, including PubMed, Embase, Web of Science and CNKI. We collected relevant articles to explore the association between the expression levels of UCA1 and prognosis., Conclusions: High expression level of UCA1 was associated with poor clinical outcome. UCA1 could serve as a novel biomarker for prognosis and might be a potential predictive factor for clinicopathological characteristics in various cancers. Further studies should be performed to verify the clinical utility of UCA1 in human solid tumors., Competing Interests: The authors declared that there are no conflicts of interest regarding the publication of this paper.

Human urothelial carcinoma associated 1 (UCA1) is a long noncoding RNA that is putatively oncogenic in solid tumors. This meta-analysis investigated an association between UCA1 levels and survival times of cancer patients. The primary endpoints were overall survival (OS) and progression-free survival (PFS). A comprehensive, computerized literature search was conducted of the databases PubMed, EMBASE, Chinese National Knowledge Infrastructure (CNKI), and Wanfang. The strength of association between UCA1 and cancer prognosis was assessed by computing the hazard ratio (HR) with its corresponding 95% confidence interval (CI). Twelve studies comprising 954 cancer patients met the criteria for this meta-analysis. Overall, a significant negative association was found between UCA1 levels and OS time (HR1.81, 95% CI1.52-2.17), including the following cancers analyzed independently: colorectal (HR2.61, 95% CI1.56-4.37), non-small cell lung (HR1.49, 95% CI1.16-1.90), gastric (HR2.19, 95% CI1.36-3.51), and ovarian (HR1.89, 95% CI1.14-3.12). There was also a significant negative association between UCA1 levels and PFS time (HR2.59, 95% CI1.61-4.16). In conclusion, this meta-analysis indicated that higher levels of UCA1 correlate with shorter PFS and OS times in cancers., Competing Interests: None.

This study aimed to investigate the expression levels of urothelial carcinoma associated 1 (UCA1) in cancer tissues and plasma of colon cancer patients, and evaluate its clinical significance. Quantitative real-time PCR was used to determine the expression levels of UCA1 in 80 pairs of colon cancer and adjacent normal tissues, plasma samples from 20 healthy controls, 20 colon cancer patients before and after tumor removal. The relationships between UCA1 expression and clinical features and overall survival were analyzed. Compared with adjacent normal tissues, UCA1 was significantly upregulated in colon cancer tissues, especially in cases with LNM and advanced TNM stages (P < 0.05). High UCA1 expression was associated with LMN, higher pT category, and advanced TNM stages (P < 0.05). Patients with high UCA1 expression had worse survival time than those with low UCA1 expression (adjusted HR = 2.002, 95% CI 1.007-3.981, P = 0.048). Furthermore, plasma levels of UCA1 in colon cancer patients were significantly higher than those of controls (P = 0.016). There was significant difference in plasma level of UCA1 between samples taken before and after surgery (P = 0.048). In conclusion, tissue expression of UCA1 is related to prognosis in colon cancer. Plasma UCA1 may serve as a potential biomarker for early diagnosis and disease monitoring of colon cancer patients.

Objective: Long non-coding ribonucleic acid urothelial carcinoma-associated 1 has been found to be a participant in cancer development and glucose metabolism in bladder cancer. However, the role of urothelial carcinoma-associated 1 in metabolic reprogramming in cancer remains to be clarified. In this study, we aim to elucidate the molecular mechanism underlying the regulation of glutamine metabolism by urothelial carcinoma-associated 1 in bladder cancer., Methods: The RNA levels of urothelial carcinoma-associated 1, GLS2 and miR-16 in bladder tissues and cell lines were examined by real-time reverse transcriptase-polymerase chain reaction. The protein levels of GLS2 were detected by western blot analysis. Reactive oxygen species generation was examined by the fluorescein isothiocyanate mean value and fluorescence microscope. Glutamine consumption was analyzed using the glutamine assay kit. Additionally, we performed luciferase reporter assays to validate urothelial carcinoma-associated 1 sequence whether contains miR-16 binding site and the interaction between the 3'UTR sequence of GLS2 and mature miR-16., Results: Real-time reverse transcriptase-polymerase chain reaction demonstrated that the RNA level of urothelial carcinoma-associated 1 and GLS2 was positively correlated in bladder cancer tissues and cell lines. The expression of GLS2 mRNA and protein increased in cells which overexpression of urothelial carcinoma-associated 1 and decreased in cells which knocked-down of urothelial carcinoma-associated 1 cell lines. urothelial carcinoma-associated 1 reduced ROS production, and promoted mitochondrial glutaminolysis in human bladder cancer cells. Furthermore, luciferase reporter assays indicated that there was a miR-16 binding site in urothelial carcinoma-associated 1, and it showed appreciable levels of sponge effects on miR-16 as readouts in a dose-dependent manner. Moreover, the 'seed region' of miR-16 directly bound to the 3'UTR of GLS2 mRNA and regulated GLS2 expression level., Conclusions: Together, our results revealed that urothelial carcinoma-associated 1 regulated the expression of GLS2 through interfering with miR-16, and repressed ROS formation in bladder cancer cells., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Gastric cancer (GC) is one of the most common malignancies and ranks the second leading cause of cancer death worldwide. The role of long non-coding RNAs (lncRNAs) in the gastric cancer pathogenesis is largely unknown. The present study is aimed to identify aberrantly expressed lncRNAs involved in the progression of GC. 33 lncRNAs showed significantly differential expression levels between gastric tumor samples and matched normal tissues from 5 pairs of samples using microarray assay. LncRNAs were classified into different subgroups. The expression levels of 4 lncRNAs: HIF1A-AS1, PVT1, CBR3-AS1 and UCA1 both in tumor and plasma were further confirmed in 20 gastric patients by real-time PCR assay. Then, the correlations between the tissue and plasma of these 4 lncRNA levels were assessed. Our data show that there was a significantly positive correlation of UCA1 expression levels between tumor tissues and plasma (r = 0.931). Furthermore, the specificity and sensitivity of PVT-1 and UCA1 were evaluated by receiver operating characteristic (ROC) curve. The results demonstrated that plasma UCA1 provided the higher diagnostic performance for detection of GC (AUC = 0.928; P < 0.001) than PVT-1 (AUC = 0.731; P < 0.01). Taken together, our study suggested that plasma UCA1 levels could be a promising candidate of noninvasive biomarker for GC early diagnosis.

The aim of this study was to explore the role of long non-coding RNA UCA1 (urothelial cancer-associated 1) in acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in EGFR-mutant non-small cell lung cancer (NSCLC). In our study, UCA1 expression was significantly increased in lung cancer cells and patients with acquired resistance to EGFR-TKIs. Over-expression of UCA1 was significantly associated with a shorter progression-free survival (PFS) [13.0 vs. 8.5 months, P < 0.01] in tumors with respond to EGFR-TKIs. The significant relationship was not observed in patients with T790M mutation (10.5 vs. 12.0 months, P = 0.778), but in patients with non-T790M (19.0 vs. 9.0 months, P = 0.023). UCA1 knockdown restored gefitinib sensitivity in acquired resistant cells with non-T790M and inhibited the activation of the AKT/mTOR pathway and epithelial-mesenchymal transition (EMT). The mTOR inhibitor was effective in UCA1-expressing cell PC9/R. Inhibiting mTOR could change the expression of UCA1, although there was no significant difference. In conclusion, the influence of over-expression of UCA1 on PFS for patients with acquired resistance to EGFR-TKIs was from the subgroup with non-T790M mutation. UCA1 may induce non-T790M acquired resistance to EGFR-TKIs by activating the AKT/mTOR pathway and EMT.

Long non-coding RNAs (lncRNAs) UCA1 have been shown to paly an important regulatory roles in cancer biology, and UCA1 dysfunction is related to TNM stage, metastasis and postoperative survival in several cancers. However, the biological role and clinical significance of UCA1 in the carcinogenesis of prostate cancer (PC) remain largely unclear. Herein, we found that UCA1 was abnormally upregulated in tumor tissues from PC patients, and patients with high UCA1 levels had a significantly poorer prognosis. Intriguingly, the mRNA and protein levels of KLF4 were significantly increased in tumor tissues, which was highly correlated to UCA1 levels. Moreover, UCA1 depletion inhibited the growth and induced apoptosis in PC3 and LNCaP cell lines. In addition, UCA1 loss-of-function could decrease KLF4 expression, subsequently, the downregulation of KRT6 and KRT13. Taken together, our study indicated that UCA1 had a crucial role in the tumorigenesis of PC. Moreover, UCA1 loss-of-function inhibited cell proliferation and induced cell apoptosis, at least partially, through inactivation KLF4-KRT6/13 cascade.

There is now considerable evidence supporting the view that macrophage infiltration is playing a critical role in the proliferation and progression of breast cancer but the underlying molecular mechanisms remain largely unknown. To this end, using long non-coding RNA (lncRNA) expression profiling, we examined changes in lncRNA expression in breast cancer cells treated with conditioned medium (CM) from cultured human THP-1 macrophages. We found that treatment with macrophage CM induced the expression of numerous lncRNAs, including urothelial cancer associated 1 (UCA1). Knockdown of UCA1 using shRNA inhibited AKT phosphorylation and abolished invasiveness of tumor cells induced by macrophage CM. Consistent with these results; we further showed that UCA1 level was significantly enhanced in human primary breast tumors and correlated with advanced clinical stage, supporting its role in promoting carcinogenesis and progression of breast cancer. Together, these results suggest that macrophage could promote invasiveness of breast cancer cells by enhancing expression of lncRNA UCA1.

Accumulating evidences indicate that different long non-coding RNAs (lncRNAs) might play a relevant role in tumorigenesis, with their expression and function already associated to cancer development and progression. CCAAT/enhancer-binding protein-α (CEBPA) is a critical regulator of myeloid differentiation whose inactivation contributes to the development of acute myeloid leukemia (AML). Mutations in C/EBPα occur in around 10% of AML cases, leading to the expression of a 30-kDa dominant negative isoform (C/EBPα-p30). In this study, we identified the oncogenic urothelial carcinoma associated 1 (UCA1) lncRNA as a novel target of the C/EBPα-p30. We show that wild-type C/EBPα and C/EBPα-p30 isoform can bind the UCA1 promoter but have opposite effects on UCA1 expression. While wild-type C/EBPα represses, C/EBPα-p30 can induce UCA1 transcription. Notably, we also show that UCA1 expression increases in cytogenetically normal AML cases carrying biallelic CEBPA mutations. Furthermore, we demonstrate that UCA1 sustains proliferation of AML cells by repressing the expression of the cell cycle regulator p27kip1. Thus, we identified, for the first time, an oncogenic lncRNA functioning in concert with the dominant negative isoform of C/EBPα in AML.

Objective: Long non-coding RNAs (lncRNAs) have been shown to play an important regulatory roles in cancer biology, and the lncRNA-UCA1 is upregulated in several cancers such as bladder cancer, breast cancer and colorectal cancer, however, the contributions of UCA1 to non-small cell lung cancer (NSCLC) remain largely unknown., Methods: Expression levels of lncRNA-UCA1 in tumor tissues and plasma from NSCLC patients was evaluated by quantitative real-time PCR, and its association with overall survival of patients was analyzed by statistical analysis. Moreover, the UCA1 expression correlation between tumor tissues and plasma was demonstrated by linear regression analysis., Results: the results showed that the expression of UCA1 in NSCLC tissues was obviously higher than that observed in pair-matched adjacent nontumourous tissues, (P < 0.001). The agarose gel electrophoretogram of RT-PCR products further confirmed that UCA1 was increased in NSCLC tissues. To assess the correlation of UCA1 expression with Clinicopathological data, we found that the expression level of UCA1 was associate with histological grade (P < 0.001) and lymph node metastasis (P < 0.001). Intriguingly, the expression of UCA1 was significantly increased in plasma from NSCLC patients. The UCA1 expression measurements obtained from plasma and tumor tissues were strongly correlated in 60 patient samples (r = 0.881). By receiver operating characteristic curve (ROC) analysis, plasma UCA1 provided the highly diagnostic performance for detection of NSCLC (the area under the ROC curve (AUC), 0.886; P < 0.001). In conclusion, the current results indicated that Plasma UCA1 could serve as a potential biomarker for diagnosis of NSCLC. UCA1 as a biomarker in clinical application might significantly improve the efficacy of human NSCLC screening.

The therapeutic potential of cisplatin in ovarian cancer treatment is restricted by the occurrence of cellular resistance. We aimed to explore the role of SRPK1 in cisplatin resistance related to the long non-coding RNA UCA1 in ovarian cancer cell.Totally, 24 ovarian cancer tissues and 16 normal tissues were used to assess the expression of UCA1 RNA. UCA1 stable transfected SKOV3 cells were established and the ability of cell migration, invasion and cisplatin resistance was assessed. The expression of SRPK1 and apoptosis pathway proteins was then assessed to explore the mechanism. In addition, SRPK1 knockdown cell line was also established and the effects of SRPK1 on cell migration, invasion and cisplatin resistance was evaluated.Elevated expression of UCA1 RNA was identified in ovarian cancer tissues compared with normal tissues. Expression of UCA1 RNA in SKOV3 cells enhanced the cell migration, invasion and cisplatin resistance. Increased expression of SRPK1 and anti-apoptosis proteins were found in SKOV3/pcDNA-UCA1 cells. Knocking-down SRPK1 could partly rescue the effect of UCA1 expression on cell migration, invasion and cisplatin resistance in SKOV3 cells.Elevated expression of UCA1 RNA was found in ovarian cancer tissues. UCA1 can improve the cell migration, invasion and induce cisplatin resistance. SRPK1 and apoptosis pathway proteins may be involved in the effect of UCA1.

The long non-coding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) has been recently shown to be dysregulated, which plays an important role in the progression of several cancers. However, the biological role and clinical significance of UCA1 in the carcinogenesis of hepatocellular carcinoma (HCC) remain unclear. Herein, we found that UCA1 was aberrantly upregulated in HCC tissues and associated with TNM stage, metastasis and postoperative survival. UCA1 depletion inhibited the growth and metastasis of HCC cell lines in vitro and in vivo. Furthermore, UCA1 could act as an endogenous sponge by directly binding to miR-216b and downregulation miR-216b expression. In addition, UCA1 could reverse the inhibitory effect of miR-216b on the growth and metastasis of HCC cells, which might be involved in the derepression of fibroblast growth factor receptor 1 (FGFR1) expression, a target gene of miR-216b, and the activation of ERK signaling pathway. Taken together, our data highlights the pivotal role of UCA1 in the tumorigenesis of HCC. Moreover, the present study elucidates a novel lncRNA-miRNA-mRNA regulatory network that is UCA1-miR-216b-FGFR1-ERK signaling pathway in HCC, which may help to lead a better understanding the pathogenesis of HCC and probe the feasibility of lncRNA-directed diagnosis and therapy for this deadly disease.

Gastric cancer ranks the second highest death rate and is the highest morbidity digestive system malignancy in China. Few reports have elucidated the role of long non-coding RNAs (lncRNAs) in the gastric cancer pathogenesis. The present study was aimed to identify aberrantly expressed lncRNAs involved in the progression of gastric cancer and explored their potential functions. A total of 1,297 lncRNAs and 2,037 mRNAs that showed significantly differential expression level between gastric tumor samples and matched adjacent normal tissues were identified in six pairs of samples using microarray assay. To further explore their functions, lncRNAs were classified into different subgroups and mRNAs were clustered into several pathways. The expression level of 4 lncRNAs: UCA1, lincRNA-BBOX1-2, CR594506 and BC015134 were further confirmed in another cohort of 10 gastric patients by real-time PCR assay. A coding-non-coding co-expression network revealed that the four validated lncRNAs were correlated with twenty-six mRNAs which gave clues about the potential roles of these lncRNAs in the process of gastric cancer progression.

Introduction: Long non-coding RNAs (lncRNAs) have been shown to have important regulatory roles in cancer biology, and the lncRNA UCA1 is upregulated in several cancers such as bladder cancer, breast cancer and colorectal cancer, however, the contributions of UCA1 to esophageal cancer remain largely unknown., Methods: Expression levels of lncRNA UCA1 in esophageal squamous cell carcinoma (ESCC) patients and esophageal cancer cell lines were evaluated by quantitative real-time PCR (qRT-PCR), and its association with overall survival of patients was analyzed by statistical analysis. Small interfering RNA was used to suppress UCA1 expression in esophageal cancer cell line. In vitro assays were conducted to further explore its underlying roles in tumor progression., Results: The relative level of UCA1 was significantly higher in ESCC tissues compared to the adjacent non-tumor tissues, and remarkably higher expression of UCA1 was found in esophageal cancer cell lines compared with the immortalized esophageal epithelial cell line NE1. The ESCC patients with higher UCA1 expression had an advanced clinical stage and a poorer prognosis than those with lower expression. In vitro assays, our data indicated that downregulation of UCA1 decrease cell proliferation, migration, and invasion ability., Conclusions: lncRNA UCA1 might be considered as a novel molecule involved in ESCC progression, which provides a potential prognostic biomarker and therapeutic target.