Urothelial Carcinoma Associated 1 Research Articles

Combinatorial Gene Expression Profiling of Serum HULC, HOTAIR, and UCA1 lncRNAs to Differentiate Hepatocellular Carcinoma from Liver Diseases: A Systematic Review and Meta-Analysis.

Hepatocellular carcinoma (HCC) presents a significant global health challenge due to limited early detection methods, primarily relying on conventional approaches like imaging and alpha-fetoprotein (AFP). Although non-coding RNAs (ncRNAs) show promise as potential biomarkers in HCC, their true utility remains uncertain. We conducted a comprehensive review of 76 articles, analyzing 88 circulating lncRNAs in 6426 HCC patients. However, the lack of a standardized workflow protocol has hampered holistic comparisons across the literature. Consequently, we herein confined our meta-analysis to only a subset of these lncRNAs. The combined analysis of serum highly upregulated in liver cancer (HULC) gene expression with homeobox transcript antisense intergenic RNA (HOTAIR) and urothelial carcinoma-associated 1 (UCA1) demonstrated markedly enhanced sensitivity and specificity in diagnostic capability compared to traditional biomarkers or other ncRNAs. These findings could have substantial implications for the early diagnosis and tailored treatment of HCC.

LncRNA UCA1 promotes tumor progression by targeting SMARCD3 in cervical cancer.

Long noncoding RNA urothelial carcinoma associated 1(UCA1) has been identified as a key molecule in human cancers. However, its functional implications remain unspecified in the context of cervical cancer (CC). This research aims to identify the regulatory mechanism of UCA1 in CC. UCA1 was identified through microarray and confirmed through a quantitative real-time polymerase chain reaction. Proteins that bind with UCA1 were recognized using RNA pull-down assays along with RNA immunoprecipitation. Ubiquitination assays and coimmunoprecipitation were performed to explore the molecular mechanisms of the SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily d, member 3 (SMARCD3) downregulated in CC. The effects of UCA1 and SMARCD3 on the progression of CC were investigated through gain- and loss-of-function assays and xenograft tumor formation in vivo. In this study, UCA1 was found to be upregulated in CC cells as well as in human plasma exosomes for the first time. Functional studies indicated that UCA1 promotes CC progression. Mechanically, UCA1 downregulated the SMARCD3 protein stabilization by promoting SMARCD3 ubiquitination. Taken together, we revealed that the UCA1/SMARCD3 axis promoted CC progression, which could provide a new therapeutic target for CC.

Long Noncoding RNA UCA1 Correlates With Electropathology in Patients With Atrial Fibrillation

BackgroundPerpetuation of atrial fibrillation (AF) is rooted in derailment of molecular proteostasis pathways that cause electrical conduction disorders that drive AF. Emerging evidence indicates a role for long noncoding RNAs (lncRNAs) in the pathophysiology of cardiac diseases, including AF. ObjectivesIn the present study, the authors explored the association between 3 cardiac lncRNAs and the degree of electropathology. MethodsPatients had paroxysmal AF (ParAF) (n = 59), persistent AF (PerAF) (n = 56), or normal sinus rhythm without a history of AF (SR) (n = 70). The relative expression levels of urothelial carcinoma–associated 1 (UCA1), OXCT1-AS1 (SARRAH), and the mitochondrial lncRNA uc022bqs.q (LIPCAR) were measured by means of quantitative reverse-transcription polymerase chain reaction in the right atrial appendage (RAA) or serum (or both). A selection of the patients was subjected to high-resolution epicardial mapping to evaluate electrophysiologic features during SR. ResultsThe expression levels of SARRAH and LIPCAR were decreased in RAAs of all AF patients compared with SR. Also, in RAAs, UCA1 levels significantly correlated with the percentage of conduction block and delay, and inversely with conduction velocity, indicating that UCA1 levels in RAA reflect the degree of electrophysiologic disorders. Moreover, in serum samples, SARRAH and UCA1 levels were increased in the total AF group and ParAF patients compared with SR. ConclusionsLncRNAs SARRAH and LIPCAR are reduced in RAA of AF patients, and UCA1 levels correlate with electrophysiologic conduction abnormalities. Thus, RAA UCA1 levels may aid staging of electropathology severity and act as a patient-tailored bioelectrical fingerprint.

Abstract 1291: Signaling pathways modulated by lncRNA UCA1 during anchorage-independent growth in colorectal cancer

Abstract Colorectal cancer (CRC) is the second deadliest cancer, and over 40-50% of patients develop metastasis during their fight against the disease. CRC survival rate drops from 90% to 14% when the condition is contained within the colon vs. when found at distant sites within the body. Metastasis is a multistep process and one of the critical steps for cancer cells to acquire anoikis resistance to survive after detachment from the primary sites and travel through the circulatory and lymphatic systems to distant target organs. Thus, understanding the molecular players involved in the anoikis process and metastasis could be vital for improving the survival of CRC patients. The aberrant expression of a long noncoding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) has been identified in CRC. However, its role in metastasis processes is not yet well defined. Our preliminary results in the anchorage-independent growth (anoikis model) demonstrate increased expression of lncRNA UCA1. Moreover, the overexpression of lncRNA UCA1 led to high expression of stemness markers SOX2 and Kaiso, along with increased survival of anchorage-independent cells, which indicates a potential mechanistic role of UCA1 in anoikis resistance. Thus, in this study, we propose elucidating the role(s) of UCA1 and its associated signaling pathways during anoikis resistance. We hypothesize that the overexpression of lncRNA UCA1 enhances CRC metastasis through anoikis resistance-associated signaling pathways. We will utilize Isogenic CRC cell lines SW480 (oncogenic) and SW620 (metastatic) to understand the mechanistic regulation of anoikis resistance. Lentiviral transduced stable overexpression (SW480+UCA1//GFP) and knockdown (SW620+CRISPRgUCA1) cell lines have been utilized for this study. After subjecting these cell lines (along with control) to anchorage-independent growth conditions, cell cycle, pro-survival, anti-apoptotic, stemness, and glucose metabolism factors will be analyzed through RT-PCR, Digital Droplet PCR (ddPCR), western blot, and FACS analyses. Utilizing the same model, we will examine lncRNA UCA1 linked anoikis resistance specific phosphorylation profiles of kinases, their protein substrates using the Proteome Profiler Phospho-Human Phospho-Kinase Array. Citation Format: Sophia Leslie, Kyle D. Doxtater, Samantha Lopez, Kristopher Ezell, Adithya Anilkumar, Amayrani Sanchez, Bilal Hafeez, Tamer Oraby, Meena Jaggi, Timothy Loy, Subhash Chauhan, Manish K. Tripathi. Signaling pathways modulated by lncRNA UCA1 during anchorage-independent growth in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1291.

Clinical Value and Mechanism of Long Non-Coding RNA UCA1 in Acute Respiratory Distress Syndrome Induced by Cardiopulmonary Bypass.

Long non-coding RNA (lncRNA) can be used as a biological marker for the diagnosis and treatment of various diseases. The study aimed to detect changes in the expression of lncRNA for urothelial carcinoma associated 1 (UCA1) in patients with cardiopulmonary bypass (CPB)-induced acute respiratory distress syndrome (ARDS). Clinical values and cell function in ARDS were explored. In total, 195 patients without CPB-induced ARDS were included in the control group, and 85 patients with ARDS were included in the ARDS group. Serum UCA1 levels were measured by quantitative real-time polymerase chain reaction. A549 was used for the cell experiments by establishing oxygen-glucose deprivation/reperfusion (OGD/R) cell models, and the cell viability and apoptosis were tested. The concentration of inflammatory factors was tested by an enzyme-linked immunosorbent assay. A luciferase reporting assay was applied for target gene analysis. Quantitative real-time polymerase chain reaction revealed a gradual increase in serum UCA1 in both control and ARDS cases, and patients with ARDS had higher levels of UCA1 than those in the control group. Serum UCA1 was positively correlated with serum tumour necrosis factor-α and interleukin-6 concentration in patients with ARDS. UCA1 had the ability to distinguish patients with ARDS fromthose without it. UCA1 inhibition protected against lung injury and inhibited cell inflammation invitro. MicroRNA (miR-182-5p) was downregulated in OGD/R-induced cell models and sponged by UCA1. Elevated expression of UCA1 may be associated with the occurrence of ARDS after CPB surgery. The regulatory role of UCA1 in ARDS might be related to inflammation and downregulated miR-182-5p in alveolar epithelial cells.

[Effects of lncRNA-UCA1 targeting miR-204-5p on the proliferation, migration, apoptosis and immune escape of endometrial carcinoma cells].

Objective: To investigate the effect of long non-coding RNA urothelial carcinoma-associated 1 (UCA1) gene on the proliferation, migration, apoptosis and immune escape of endometrial cancer cells and its molecular mechanism. Methods: Endometrial cancer tissues and adjacent normal tissues of patients with endometrioid adenocarcinoma who underwent total or partial hysterectomy in Henan Provincial People's Hospital from 2017 to 2019 were collected. The expressions of UCA1 and miR-204-5p were detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR), and the cell proliferation, migration and apoptosis were detected by cell counting kit 8 (CCK8) method, Transwell method, flow cytometry, and dual-luciferase reporter assay was used to explore the target relationship between UCA1 and miR-204-5p. HEC-1A-sh-NC or HEC-1A-sh-UCA1 cells were co-cultured with peripheral blood mononuclear cells (PBMC) or cytokine-induced killer cells in vitro to explore the role of UCA1 in immune escape. Results: The expression level of UCA1 in endometrial cancer tissue (17.08±0.84) was higher than that in adjacent normal endometrial tissue (3.00±0.37), and the expression level of miR-204-5p (0.98±0.16) was lower than that in adjacent normal endometrial tissue (2.00±0.20, P<0.05). Pearson correlation analysis showed that the expression of miR-204-5p was negatively correlated with the expression of UCA1 (r=-0.330, P=0.030). The expressions of UCA1 and miR-204-5p were associated with the International Federation of Gynecology and Obstetrics stage of endometrial cancer, lymph node metastasis and vascular invasion (P<0.05). The relative ratio of absorbance (0.58±0.11) and the number of cell migration [(199.68±18.44)] in the sh-UCA1 group were lower than those in the sh-NC group (1.24±0.17 and 374.76±24.83), respectively. The apoptosis rate of sh-UCA1 group [(28.64±7.80)%] was higher than that of sh-NC group [(14.27±4.38)%, P<0.05]. After different ratios of effector cells and target cells were cultured, the cell survival rate of HEC-1A-sh-UCA1 group was lower than that of HEC-1A-sh-NC group, and the difference was statistically significant (P<0.05). UCA1 had a binding site for miR-204-5p. The relative ratio of absorbance (1.74±0.08) and the number of cell migration (426.00±18.00) cells in the UCA1+ anti-miR-204-5p group were higher than those in the control group [1.00±0.03 and (284.00±8.00) cells, respectively]. The apoptosis rate of UCA1+ anti-miR-204-5p group [(5.42±0.93)%] was lower than that of control group [(14.82±1.48)%, P<0.05]. HEC-1A-sh-UCA1 cells could induce higher interferon gamma (IFN-γ) expression when co-cultured with PBMC, and the levels of IFN-γ expression in PHA group and PHA+ pre-miR-204-5p group cells were 2.42±0.49 and 1.88±0.26, which were higher than that in the PHA+ pre-NC group (0.85±0.10, P<0.05). When co-cultured with cytokine-induced killer cells (different ratios) in vitro, the HEC-1A-sh-UCA1 group and the HEC-1A-pre-miR-204-5p group had lower survival rates than that in the HEC-1A-pre-miR-204-5p group. In the HEC-1A-pre-NC group, the differences were statistically significant (P<0.05). Conclusion: UCA1/miR-204-5p may play an important role in human endometrial cancer.

The role of UCA1 and WRAP53 in diagnosis of hepatocellular carcinoma: A single-center case-control study.

Hepatocellular carcinoma (HCC) prognosis heavily depends on early diagnosis. We aimed to determine the role of serum urothelial carcinoma-associated 1 (UCA1) and wd repeat containing antisense to TP53 (WRAP53) as diagnostic tools of HCC. A case-control study including 90 subjects (30 patients having HCC, 30 patients having liver cirrhosis without HCC and 30 healthy controls) was performed. In all participants, the serum levels of UCA1 and WRAP53 were assessed by quantitative real-time polymerase chain reaction together with serumαa-fetoprotein (AFP). Serum levels of both UCA1 and WRAP53 were upregulated in patients with HCC being significantly higher than in patients with liver cirrhosis and healthy control (p < 0.001). They were also correlated with some clinicopathological characteristics of HCC. Using the receiver operating curve, both UCA1 and WRAP53 showed higher diagnostic performance for HCC (AUC = 0.9, 73.3% sensitivity, 100% specificity and AUC = 0.85, 63.3% sensitivity, 80% specificity respectively) and their combination with AFP resulted in improved sensitivity and specificity (AUC = 0.97, 90% sensitivity, 100% specificity). Serum UCA1 and WRAP53 have the potential to be used alone, or in combination or with AFP, as diagnostic non-invasive biomarkers for HCC with accepted sensitivity and specificity. This study has been registered in clinicaltrials.gov with clinical trial registration number NCT05088811.

Long non-coding RNA UCA1 regulates MPP+-induced neuronal damage through the miR-671-5p/KPNA4 pathway in SK-N-SH cells.

Parkinson's disease (PD) is an age-related neurodegenerative disease. Long non-coding RNA urothelial carcinoma-associated 1 (UCA1) is involved in the pathogenesis of PD. However, the pathogenesis of PD regulated by UCA1 has not been fully explained. We used 1-Methyl-4-phenylpyridinium (MPP+)-induced SK-N-SH cells for functional analysis. Expression levels of UCA1, microRNA (miR)-671-5p, and KPNA4 (karyopherin subunit alpha 4) mRNA were detected using quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability and apoptosis were analyzed using MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) or flow cytometry assays. Some protein levels were measured by western blotting. The levels of pro-inflammatory cytokines were tested by ELISA (enzyme-linked immunosorbent assay). The levels of LDH (lactate dehydrogenase), MDA (malondialdehyde), and SOD (superoxide dismutase) were measured using corresponding kits. The relationship between UCA1 or KPNA4 and miR-671-5p was verified by dual-luciferase reporter assay and/or RNA immunoprecipitation (RIP) assay. MPP+ induced UCA1 expression in SK-N-SH cells in a concentration-dependent manner or time-dependent manner. UCA1 knockdown reduced MPP+-induced apoptosis, inflammation, and oxidative stress in SK-N-SH cells. MiR-671-5p was downregulated while KPNA4 was upregulated in MPP+-treated SK-N-SH cells. UCA1 sponged miR-671-5p to regulate KPNA4 expression. MiR-671-5p inhibition counteracted UCA1 knockdown-mediated influence on apoptosis, inflammation, and oxidative stress of MPP+-induced SK-N-SH cells. KPNA4 overexpression offset the inhibitory influence of miR-671-5p mimic on apoptosis, inflammation, and oxidative stress of MPP+-treated SK-N-SH cells. UCA1 inhibition reduced MPP+-induced neuronal damage through the miR-671-5p/KPNA4 pathway in SK-N-SH cells, providing a novel mechanism to understand the pathogenesis of PD.

Long noncoding RNA UCA1 promotes the expression and function of P-glycoprotein by sponging miR-16-5p in human placental BeWo cells.

Investigations on placental P-glycoprotein (P-gp) regulation could provide more therapeutic targets for individualized and safe pharmacotherapy during pregnancy. The role of long noncoding RNA (lncRNA) on placental P-gp regulation is lacking. The present study was carried out to investigate the regulation and underlying mechanisms of lncRNA urothelial carcinoma associated 1 (UCA1) on P-gp in Bewo cells. lncRNA UCA1 inhibition or overexpression could decrease or increase ABCB1 mRNA expression, P-gp expression and its cellular efflux function, respectively. RNA-FISH revealed that lncRNA UCA1 was mainly located in the cytoplasm of Bewo cells. MicroRNA array was applied and 10 significant miRNAs was identified after lncRNA UCA1 inhibition. Databases of LncTarD, LncRNA2Target, and miRcode were further used to search potential target miRNAs of lncRNA UCA1 and miR-16-5p was screened out. Thereafter, we confirmed that miR-16-5p expression was significantly upregulated or reduced after lncRNA UCA1 knockdown or overexpression, respectively. Furthermore, we also proved that ABCB1 mRNA expression, P-gp expression and its cellular efflux function was enhanced or reduced after miR-16-5p inhibition or overexpression, respectively. The rescue experiment further indicated that miR-16-5p was involved in the positive regulation of lncRNA UCA1 on the expression and function of P-gp. Lastly, dual-luciferase reporter system, RNA-binding protein immunoprecipitation and RNA pull-down assays were performed to explore the relationships among lncRNA UCA1, miR-16-5p, and ABCB1. It was found that lncRNA UCA1(1103-1125) could directly interact with miR-16-5p and miR-16-5p could directly target ABCB1 coding DNA sequence region (882-907). In conclusion, LncRNA UCA1 could promote the expression and function of P-gp by sponging miR-16-5p in BeWo cells.

LncRNA UCA1 epigenetically suppresses APAF1 expression to mediate the protective effect of sevoflurane against myocardial ischemia-reperfusion injury.

Myocardial ischemia-reperfusion injury (MI/RI) is a leading cause of death globally. Whereas some long noncoding RNAs (lncRNAs) are known to participate in the progression of MI/RI, the role of urothelial carcinoma associated 1 (UCA1) in conjunction with sevoflurane treatment remains largely unknown. H9C2 cardiomyocytes were subjected to hypoxia/reoxygenation (H/R) to establish an in vitro MI/RI model, and sevoflurane was then added. Cell viability, apoptosis, SOD activity, and MDA levels were measured. Levels of inflammatory cytokines and methylation of apoptosis protease-activating factor 1 (APAF1) were determined. Interactions among lncRNA UCA1, enhancer of zeste homologue 2 (EZH2), DNA methyltransferase-1 (DNMT1), and APAF1 were analyzed. After H/R treatment, the viability of H9C2 cardiomyocytes decreased and apoptosis rate, oxidative stress factor levels, inflammatory cytokine levels, and apoptosis-related protein levels all increased. Sevoflurane treatment reversed these changes. LncRNA UCA1 knockdown attenuated the therapeutic effect of sevoflurane on H/R-treated cardiomyocytes, and silencing of APAF1 reversed this role of UCA1 knockdown. Moreover, lncRNA UCA1 recruited DNMT1 through EZH2, thus promoting methylation of the APAF1 promoter region. LncRNA UCA1 recruits DNMT1 to promote methylation of the APAF1 promoter through EZH2, thus strengthening the protective effect of sevoflurane on H/R-induced cardiomyocyte injury.

LncRNA UCA1 mediates Cetuximab resistance in Colorectal Cancer via the MiR-495 and HGF/c-MET Pathways.

Background: Cetuximab is one of the most widely used monoclonal antibodies to treat patients with RAS/BRAF wild-type metastatic colorectal cancer (mCRC). Unfortunately, cetuximab resistance often occurs during targeted therapy. However, the underlying epigenetic mechanisms remain unclear. Our previous study demonstrated that the exosomal transfer of urothelial carcinoma-associated 1 (UCA1) confers cetuximab resistance to CRC cells. The goal of this study was to elucidate the detailed role of UCA1 in cetuximab resistance in CRC and the underlying molecular mechanism.Methods: In vitro and in vivo functional studies were performed to assess the role of UCA1 in cetuximab resistance in CRC cell lines and xenograft models. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to examine UCA1 localization and expression. Bioinformatics analysis was performed to predict the potential mechanism of UCA1, which was further validated by the dual-luciferase reporter assay and the RNA immunoprecipitation (RIP) assay. Cells treated with indicators were subjected to Cell Counting Kit-8 (CCK-8) and western blotting to investigate the role of hepatocyte growth factor (HGF)/c-mesenchymal-epithelial transition (c-MET) signalling in UCA1-mediated cetuximab resistance.Results: We showed that UCA1 decreased CRC cell sensitivity to cetuximab by suppressing apoptosis. Mechanistic studies revealed that UCA1 promoted cetuximab resistance by competitively binding miR-495 to facilitate HGF and c-MET expression in CRC cells. Moreover, HGF was shown to attenuate the cetuximab-induced inhibition of cell proliferation by activating the HGF/c-MET pathway in CRC cells.Conclusion: We provide the first evidence of a UCA1-miR-495-HGF/c-MET regulatory network involved in cetuximab resistance in CRC. Therefore, UCA1 has potential as a predictor and therapeutic target for cetuximab resistance.

Urine Biomarkers for the Diagnosis of Bladder Cancer: a Network Meta-Analysis.

To identify effective urine biomarkers for bladder cancer diagnosis. This meta-analysis was conducted following the guidelines of the Meta-Analyses (PRISMA) statement. Relevant studies were searched from the PubMed, Embase, and Cochrane Library databases. Heterogeneity tests were performed using Q statistics and I2 tests to determine the use of the random or fixed effects model. A direct comparison meta-analysis and network meta-analysis were conducted. The effect values are presented as odds ratios and 95% confidence intervals. Sensitivity analysis and consistency tests were performed. Fifty-eight studies with 12,038 participants were included. Direct comparison meta-analysis showed statistically significant differences in bladder cancer antigen (BTA) trak vs. nuclear matrix protein 22 (NMP22), BTA stat vs. urine cytology (UC), and fluorescence in situ hybridization (FISH) vs. UC, among the sensitivity indicators. Among the specificity indicators, there were statistically significant differences in BTA trak vs. UC, ImmunoCyt (immunocyte) vs. NMP22, and BTA stat vs. FISH. Among the positive predictive indicators, NMP22 vs. UC, BTA stat vs. UC, and FISH vs. NMP22 showed statistically significant differences. Among the negative predictive indicators, the differences in FISH vs. UC, FISH vs. NMP22, and hyaluronidase 1 (HYAL-1) vs. UC were statistically significant. Among the accuracy indicators, FISH vs. NMP22, FISH vs. UC, and HYAL-1 vs. UC showed statistically significant differences. Network meta-analysis showed that HYAL-1, urothelial carcinoma associated 1 (UCA1) and survivin had the highest sensitivity, while UC had the lowest sensitivity. The specificity of UC, FISH, and HYAL-1 was the highest, while that of UCA1 was the lowest. In terms of positive predictive indicators, UC, FISH, and HYAL-1 had the highest positive predictive value, while the BTA group had the lowest positive predictive value. In terms of negative predictive indicators, HYAL-1, UCA1, and survivin had the highest negative predictive value, while UC had the lowest negative predictive value. In terms of accuracy indicators, HYAL-1, UCA1, and survivin had the highest accuracy, while UC had the lowest accuracy. HYAL-1 and survivin are suitable urine biomarkers for bladder cancer diagnosis.

Mechanistic study of lncRNA UCA1 promoting growth and cisplatin resistance in lung adenocarcinoma

AimThis study aimed to explore the mechanism of LncRNA urothelial carcinoma-associated 1 (UCA1) promoting cisplatin resistance in lung adenocarcinoma (LUAD).MethodThe UCA1 expression level in LUAD cell lines was detected by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). We overexpressed UCA1 in A549 cells and downregulated UCA1 in A549/DDP cells by the lentivirus‑mediated technique. Subsequently, in vitro, and in vivo functional experiments were performed to investigate the functional roles of UCA1 in the growth and metastasis of LUAD cell lines. Furthermore, RNA pulldown, mass spectrometry, and RNA immunoprecipitation technique were performed to analyze various downstream target factors regulated by UCA1.ResultsThe results revealed a higher UCA1 expression level in A549/DDP cells and LUAD tissues than in A549 cells and adjacent cancer tissues. UCA1 expression was significantly associated with distant metastasis, clinical stage, and survival time of patients with LUAD. UCA1 overexpression significantly increased the proliferation, invasion, clone formation, and cisplatin resistance ability and enhanced the expression levels of proliferating cell nuclear antigen and excision repair cross-complementing gene 1 in A549 cells. However, these trends were mostly reversed after the knockdown of UCA1 in A549/DDP cells. Tumorigenic assays in nude mice showed that UCA1 knockdown significantly inhibited tumor growth and reduced cisplatin resistance. Enolase 1 was the RNA-binding protein (RBP) of UCA1.ConclusionBased on the results, we concluded that UCA1 promoted LUAD progression and cisplatin resistance and hence could be a potential diagnostic marker and therapeutic target in patients with LUAD.

Long non-coding ribonucleic acid urothelial carcinoma-associated 1 promotes high glucose-induced human retinal endothelial cells angiogenesis through regulating micro-ribonucleic acid-624-3p/vascular endothelial growth factor C.

Aims/IntroductionEmerging evidence has indicated that long non‐coding ribonucleic acids play important roles in the development and progression of diabetic retinopathy (DR). It is reported that urothelial carcinoma‐associated 1 (UCA1) is highly expressed in diabetic lymphoendothelial cells and influences glucose metabolism in rats with DR. The aim of the present study was to explore the role of UCA1 in the mechanism of DR.Materials and MethodsGene expression analyses in fibrovascular membranes excised from patients with DR using public microarray datasets (GSE60436). Reverse transcription polymerase chain reaction was carried out to detect UCA1, micro‐ribonucleic acid (miR)‐624‐3p and vascular endothelial growth factor C (VEGF‐C) expressions in the blood of patients and human retinal endothelial cells (HRECs). Furthermore, Cell Counting kit‐8, Transwell assay, and tube formation assay were used to identify biological effects of UCA1 on HRECs proliferation, migration ability and angiogenesis in vitro.ResultsUCA1 and VEGF‐C were elevated in DR patients and high glucose‐induced HRECs cell lines, whereas miR‐624‐3p was decreased. UCA1 inhibition inhibited proliferation, angiogenesis and migration of HRECs cells under high‐glucose condition. Luciferase reporter assay showed that UCA1 could sponge with miR‐624‐3p, which could directly target VEGF‐C. Finally, we proved a pathway that UCA1 promoted cell proliferation, migration and angiogenesis through sponging with miR‐624‐3p, thereby upregulating VEGF‐C in high‐glucose‐induced HRECs.ConclusionsWe identified UCA1 as an important factor associated with DR, which could regulate the expression of VEGF‐C by sponging miR‐624‐3p in human retinal endothelial cells. Our results pave the way for further studies on diagnostic and therapeutic studies related to UCA1 in DR patients.

Circulating lncRNA UCA1 and lncRNA PGM5-AS1 act as potential diagnostic biomarkers for early-stage colorectal cancer.

Background: Colorectal cancer (CRC) is one of the most common and significant malignant diseases worldwide. In the present study, we evaluated two long non-coding RNAs (lncRNAs) in CRC patients as diagnostic markers for early-stage CRC.Methods: Using Gene Expression Omnibus (GEO) datasets GSE102340, GSE126092, GSE109454 and GSE115856, 14 differentially expressed lncRNAs were identified between cancer and adjacent tissues, among which, the two most differentially expressed were confirmed using quantitative real-time polymerase chain reaction (qRT-PCR) in 200 healthy controls and 188 CRC patients. A receiver operating characteristic (ROC) analysis was employed to evaluate the diagnostic accuracy for CRC.Results: From four GEO datasets, three up-regulated and eleven down-regulated lncRNAs were identified in CRC tissues, among which, lncRNA urothelial carcinoma-associated 1 (UCA1) and lncRNA phosphoglucomutase 5-antisense RNA 1 (PGM5-AS1) were the most significantly up- and down-regulated lncRNAs in CRC patient plasma, respectively. The area under the ROC curve was calculated to be 0.766, 0.754 and 0.798 for UCA1, PGM5-AS1 and the combination of these two lncRNAs, respectively. Moreover, the diagnostic potential of these two lncRNAs was even higher for the early stages of CRC. The combination of UCA1 and PGM5-AS1 enhanced the AUC to 0.832, and when the lncRNAs were used with carcinoembryonic antigen (CEA), the AUC was further improved to 0.874.Conclusion: In the present study, we identified two lncRNAs, UCA1 and PGM5-AS1, in CRC patients’ plasma, which have the potential to be used as diagnostic biomarkers of CRC.

LncRNA UCA1 promotes development of gastric cancer via the miR-145/MYO6 axis

BackgroundLong noncoding RNA (lncRNA), urothelial carcinoma-associated 1 (UCA1) is aberrantly expressed in multiple cancers and has been verified as an oncogene. However, the underlying mechanism of UCA1 in the development of gastric cancer is not fully understood. In the present study, we aimed to identify how UCA1 promotes gastric cancer development.MethodsThe Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) data were used to analyze UCA1 and myosin VI (MYO6) expression in gastric cancer. Western blot and quantitative real-time PCR (QPCR) were performed to test the expression level of the UCA1/miR-145/MYO6 axis in gastric cancer cell lines and tissues. The roles of the UCA1/miR-145/MYO6 axis in gastric cancer in vitro and in vivo were investigated by CCK-8 assay, flow cytometry, siRNAs, immunohistochemistry, and a mouse xenograft model. The targeted relationship among UCA1, miR-145, and MYO6 was predicted using LncBase Predicted v.2 and TargetScan online software, and then verified by luciferase activity assay and RNA immunoprecipitation.ResultsUCA1 expression was higher but miR-145 expression was lower in gastric cancer cell lines or tissues, compared to the adjacent normal cell line or normal tissues. Function analysis verified that UCA1 promoted cell proliferation and inhibited cell apoptosis in the gastric cancer cells in vitro and in vivo. Mechanistically, UCA1 could bind directly to miR-145, and MYO6 was found to be a downstream target gene of miR-145. miR-145 mimics or MYO6 siRNAs could partly reverse the effect of UCA1 on gastric cancer cells.ConclusionsUCA1 accelerated cell proliferation and inhibited cell apoptosis through sponging miR-145 to upregulate MYO6 expression in gastric cancer, indicating that the UCA1/miR-145/MYO6 axis may serve as a potential therapeutic target for gastric cancer.

UCA1 Overexpression Promotes Hypoxic Breast Cancer Cell Proliferation and Inhibits Apoptosis via HIF-1α Activation.

The noncoding RNA termed urothelial carcinoma-associated 1 (UCA1) is an oncogenic lncRNA involved in promoting the growth of several tumors through various pathways. The aim of this study was to explore the expression of UCA1 in hypoxic breast cancer and its impact on tumorigenesis in low levels of oxygen. Here, we show that UCA1 is upregulated in a number of hypoxic (1% O2) breast cancer cells. In addition, UCA1 expression is significantly overexpressed in breast cancer tissues compared to matched normal cells. UCA1 knockdown in hypoxia inhibits breast cancer proliferation and induces apoptosis. The knockdown of hypoxia-inducible transcription factor 1α (HIF-1α) but not HIF-2α significantly decreases the expression of UCA1 in hypoxia. Overall, these findings indicate that UCA1 is a hallmark of hypoxic breast cancer and its expression is positively regulated by HIF-1α.

Prognostic value of long noncoding RNA urothelial carcinoma-associated 1 in esophageal carcinoma: A protocol for meta-analysis, TCGA data and bioinformatics analysis.

Background:Currently, an increasing number of long noncoding RNAs (LncRNAs) have been reported to be abnormally expressed in human carcinomas and play a vital role in tumourigenesis. Some studies have been carried out to investigate the influence of the expression of LncRNA human urothelial carcinoma associated 1 (UCA1) on prognosis and clinical significance in patients with esophageal cancer, but the results are contradictory and uncertain. A meta-analysis and was conducted with controversial data to accurately assess the issue. We collected relevant TCGA data to further testify the result. In addition, bioinformatics analysis was conducted to investigate the mechanism and related pathways of LncRNA UCA1 in esophageal carcinoma.Methods:Wanfang, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure, the Chongqing VIP Chinese Science and Technology Periodical Database, PubMed, Embase, and Web of Science were thoroughly searched for relevant information. Two reviewers independently performed data extraction and literature quality evaluation. Odd ratio and its 95% confidence intervals were applied to evaluate the relationship between LncRNA UCA1 and clinicopathological characteristics of esophageal carcinoma patients. Hazard ratios and its 95% confidence intervals were adopted to assess the prognostic effects of LncRNA UCA1 on overall survival and disease-free survival. Meta-analysis was performed with Stata 14.0 software. To further assess the function of LncRNA UCA1 in esophageal carcinoma, relevant data from The Cancer Genome Atlas (TCGA) database was collected. Three databases, miRWalk, TargetScan, and miRDB, were used for prediction of target genes. Genes present in these 3 databases were considered as predicted target genes of LncRNA UCA1. Venny 2.1 were used for intersection analysis. Subsequently, GO, KEGG, and PPI network analysis were conducted based on the overlapping target genes of LncRNA UCA1 to explore the possible molecular mechanism in esophageal carcinoma.Results:This study provides a high-quality medical evidence for the correlation between LncRNA UCA1 expression and overall survival, and between disease-free survival and clinicopathological features. Based on bioinformatics analysis, this study enhanced the understanding of the mechanism and related pathways of LncRNA UCA1 in esophageal carcinoma.Conclusion:The study provides updated evidence to evaluate whether the expression of LncRNA UCA1 is in association with poor prognosis in patients with esophageal carcinoma.Ethics and disseminationThe private information from individuals will not be published. This systematic review also should not damage participants’ rights. Ethical approval is not available. The results may be published in a peer-reviewed journal or disseminated in relevant conferences.OSF Registration Number:DOI 10.17605/OSF.IO/8MCHW.

Long Noncoding RNA UCA1 in Gastrointestinal Cancers: Molecular Regulatory Roles and Patterns, Mechanisms, and Interactions.

The rising trend of gastrointestinal (GI) cancer has become a global burden due to its aggressive nature and poor prognosis. Long noncoding RNAs (lncRNAs) have recently been reported to be overexpressed in different GI cancers and may contribute to cancer progression and chemoresistance. They are featured with more than 200 nucleotides, commonly polyadenylated, and lacking an open reading frame. LncRNAs, particularly urothelial carcinoma-associated 1 (UCA1), are oncogenes involved in regulating cancer progression, such as cell proliferation, invasion, migration, and chemoresistance, particularly in GI cancer. This review was aimed to present an updated focus on the molecular regulatory roles and patterns of lncRNA UCA1 in progression and chemoresistance of different GI cancers, as well as deciphering the underlying mechanisms and its interactions with key molecules involved, together with a brief presentation on its diagnostic and prognostic values. The regulatory roles of lncRNA UCA1 are implicated in esophageal cancer, gastric cancer, pancreatic cancer, hepatobiliary cancer, and colorectal cancer, where they shared similar molecular mechanisms in regulating cancer phenotypes and chemoresistance. Comparatively, gastric cancer is the most intensively studied type in GI cancer. LncRNA UCA1 is implicated in biological roles of different GI cancers via interactions with various molecules, particularly microRNAs, and signaling pathways. In conclusion, lncRNA UCA1 is a potential molecular target for GI cancer, which may lead to the development of a novel chemotherapeutic agent. Hence, it also acts as a potential diagnostic and prognostic marker for GI cancer patients.

Overexpression of long non-coding RNA urothelial carcinoma associated 1 causes paclitaxel (Taxol) resistance in colorectal cancer cells by promoting glycolysis

Some colorectal cancer patients show resistance to conventional chemotherapeutic agents including Taxol. This study investigated the roles of lncRNA urothelial carcinoma-associated 1 (UCA1) in the modulation of Taxol resistance in human colorectal cancer cells. According to our results, UCA1 was significantly upregulated in colon cancer cell lines/tissues. Construction of the UCA1 overexpression vector revealed that high UCA1 expression was responsible for Taxol resistance and that Taxol can induce UCA1 expression. Importantly, Taxol-resistant cells had a higher glycolysis rate and upregulated expression of the key glycolysis enzymes hexokinase 2 (HK2) and lactate dehydrogenase A (LDHA) than Taxol-sensitive cells. Further research demonstrated that UCA1 could directly regulate glycolysis by regulating HK2 and LDHA expression, which contributes to Taxol resistance. UCA1 is a potential target to overcome chemoresistance in colorectal cancer. We report the modulation of UCA-1-regulated glycolysis as a novel anticancer strategy along with the novel role of UCA1 in Taxol resistance.