lncRNA Urothelial Carcinoma-associated 1 Research Articles

LncRNA UCA1 promotes vasculogenic mimicry by targeting miR-1-3p in gastric cancer.

Long non-coding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) has been implicated in several tumors. UCA1 promotes cell proliferation, migration and invasion of GC cells, but the molecular mechanism has not been fully elucidated. This study revealed the oncogenic effects of UCA1 on cell growth and invasion. Furthermore, UCA1 expression was significantly correlated with the overall survival of GC patients, and the clinicopathological indicators, including tumor size, depth of invasion, lymph node metastasis, and TNM stage. Additionally, miR-1-3p was identified as a downstream target of UCA1, which was negatively regulated by UCA1. MiR-1-3p inhibited cell proliferation and vasculogenic mimicry (VM), and induced cell apoptosis by upregulating BAX, BAD, and tumor suppressor TP53 expression levels. Moreover, miR-1-3p almost completely reversed the oncogenic effect caused by UCA1, including cell growth, migration and VM formation. This study also confirmed UCA1 promoted tumor growth in vivo. In this study, we also revealed the correlation between UCA1 and VM formation, which is potentially crucial for tumor metastasis. Meanwhile, its downstream target miR-1-3p inhibited VM formation in GC cells. In summary, these findings indicate that UCA1/miR-1-3p axis is potential target for GC treatment.

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.

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.

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.

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.

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.

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.

Long Noncoding RNA UCA1 Is Related to Autophagy and Apoptosis in Endometrial Stromal Cells.

Research QuestionThe expression of the long noncoding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) in embryonic tissues is higher than that in most cancer tissues, such as bladder cancer, indicating that RNA is a carcinoembryonic antigen. However, there are no published reports on the role of UCA1 in endometriosis (EMS). Therefore, to address this gap in knowledge, we assessed the potential role of lncRNA UCA1 in the pathogenesis and progression of EMS.DesignTo verify the expression of UCA1 in EMS, quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used. RNA interference (siRNA) was used to study the biological function of UCA1 in EMS in vitro.ResultsqRT-PCR analysis showed that the expression of lncRNA UCA1 in EMS was increased (P<0.01). Knockdown of UCA1 in vitro significantly inhibited the proliferation of endometrial stromal cells (ESCs) and induced autophagy and apoptosis.ConclusionUCA1 is highly expressed in EMS and promotes the proliferation of ESCs but suppresses autophagy and apoptosis. In EMS, UCA1 may be a prognostic marker and therapeutic target.

LncRNA UCA1 maintains the low-tumorigenic and nonmetastatic status by stabilizing E-cadherin in primary prostate cancer cells.

Long noncoding RNAs (LncRNAs) have emerged as important players in cancer biology. Increasing evidence suggests that LncRNAs are frequently dysregulated in cancer and may function as oncogenes or tumor suppressors. Urothelial carcinoma associated 1 (UCA1), a LncRNA, firstly identified in bladder transitional cell carcinoma, seems to act as an oncogene in many different types of human cancers by promoting cell proliferation and migration. In this study, we revealed a novel biological function of UCA1, which was different from thatreported by previous studies, was responsible for maintaining the low-tumorigenic, nonmetastatic phenotypes in primary prostate epithelial cells. UCA1 could stabilize E-cadherin protein by preventing the interaction between E-cadherin and its E3 ligase MDM2, which suppressed MDM2-mediated ubiquitination and degradation of E-cadherin. In addition, we also found that UCA1 acted as a sponge of miR-296-3p, which targeted E-cadherin gene CDH1 messenger RNA at the posttranscription level. Taken together, these findings demonstrated that UCA1 had a new important role in effectively keeping E-cadherin at a high level through a dual mechanism, which maintained primary prostate cancer cells at the low-tumorigenic and nonmetastatic status.

Erratum.

Glioma is the most common and lethal malignant intracranial tumor. Long noncoding RNAs (lncRNAs) have been identified as pivotal regulators in the tumorigenesis of glioma. However, the role of lncRNA urothelial carcinoma-associated 1 (UCA1) in glioma genesis is still unknown. The purpose of this study was to investigate the underlying function of UCA1 on glioma genesis. The results demonstrated that UCA1 was upregulated in glioma tissue and indicated a poor prognosis. UCA1 knockdown induced by si-UCA1 significantly suppressed the proliferative, migrative, and invasive activities of glioma cell lines (U87 and U251). Bioinformatics analysis and luciferase reporter assay verified the complementary binding within UCA1 and miR-122 at the 3′-UTR. Functional experiments revealed that UCA1 acted as an miR-122 “sponge” to modulate glioma cell proliferation, migration, and invasion via downregulation of miR-122. Overall, the present study demonstrated that lncRNA UCA1 acts as an endogenous sponge of miR-122 to promote glioma cell proliferation, migration, and invasion, which provides a novel insight and therapeutic target in the tumorigenesis of glioma.

Long noncoding RNA UCA1 promotes cell growth, migration, and invasion by targeting miR-143-3p in oral squamous cell carcinoma.

BackgroundThe long noncoding RNA (lncRNA) urothelial carcinoma‐associated 1 (UCA1) is dysregulated in many types of tumors; however, its role in oral squamous cell carcinoma (OSCC) remains unclear. This study aims to determine the effect of lncRNA UCA1 on OSCC.MethodsFifty‐six paired OSCC and adjacent nontumorous tissues were collected and the levels of UCA1, miR‐143‐3p, and MYO6 in the tissues were evaluated by qRT‐PCR. In in vitro experiments, cell viability, migration, and invasion were measured by, respectively, performing CCK‐8, wound healing, and transwell assays. The target relationships among UCA1, miR‐143‐3p, and MYO6 were verified by dual‐luciferase assay. Western blot and immunohistochemistry were carried out to determine the protein levels. Xenograft mouse model was established to explore the effects of UCA1 in vivo.ResultsLevels of UCA1 and MYO6 were increased significantly in OSCC, while the level of miR‐143‐3p was decreased compared with the adjacent nontumorous tissues. UCA1 promoted OSCC cell growth, migration, and invasion both in vitro and in vivo, while miR‐143‐3p reversed the progression. MYO6 was validated as a target for miR‐143‐3p, and MYO6 overexpression reversed the effects of miR‐143‐3p mimic on OSCC cells.ConclusionLncRNA UCA1 contributes to the proliferation and metastasis of OSCC cells by targeting miR‐143‐3p and upregulating its downstream gene MYO6. UCA1 could serve as a promising novel target therapy for treatment of OSCC.

Silencing of lncRNA UCA1 curbs proliferation and accelerates apoptosis by repressing SIRT1 signals by targeting miR-204 in pediatric AML.

The long noncoding RNA urothelial carcinoma-associated 1 (UCA1) has been reported to sustain the proliferation of acute myeloid leukemia (AML) cells through downregulating cell cycle regulators p27kip1 . Yet, the foundational mechanism of UCA1 in AML pathologies remains unclear. Herein, we found an escalation of UCA1 expression and suppression of miR-204 expression in pediatric AML patients and cells. UCA1 silencing suppressed cell proliferative abilities, promoted apoptotic rates, decreased Ki67, and increased cleaved caspase-3 in AML cells. Moreover, UCA1 sponged miR-204 and suppressed its expression. UCA1 overexpression inversed the miR-204 suppressed proliferation and promoted apoptosis. UCA1 also boosted the expression of SIRT1, a miR-204 target, via the sponging interaction. Furthermore, miR-204 inhibited inducible nitric oxide synthase and cyclooxygenase-2 expression, while UCA1 overexpression inversed the inhibitory effects in AML cells. Our findings concluded that UCA1 downregulation repressed cell proliferation and promoted apoptosis through inactivating SIRT1 signals by upregulating miR-204 in pediatric AML.

Modulation of TNF-α plasma levels in coronary artery disease [CAD] and non-CAD male patients by lncRNA UCA1 and aspirin

The aim of this study was to investigate the expression of long non-coding RNA urothelial carcinoma-associated 1 (UCA1) and its role in TNF-? production as one of the main inflammatory cytokines, in peripheral blood mononuclear cells (PBMCs) of patients with coronary artery disease (CAD) and healthy non-CAD (NCAD) individuals as the control group. Fifteen CAD and 15 NCAD individuals were enrolled in the study. UCA1 expression in PBMCs and the plasma concentrations of interleukin (IL)-6, IL-22 and tumor necrosis factor (TNF)-? were assessed by real-time PCR and flowcytometry, respectively. UCA1 expression was not significantly different between the CAD and NCAD groups, however, its level was higher in PBMCs of regular aspirin users of both study groups. Furthermore, aspirin users showed a significantly lower plasma level of TNF-? in comparison to non-aspirin users. In addition, UCA1 expression was negatively correlated with the level of TNF-? in the total sample of the examined population. It seems that the increased levels of UCA1 may be an underlying mechanism for downregulation of TNF-? in aspirin users.

Long non-coding RNA UCA1 promotes the progression of paclitaxel resistance in ovarian cancer by regulating the miR-654-5p/SIK2 axis.

Ovarian cancer (OC) is a common tumor in women, and the development of chemoresistance is the major obstacle to its treatment. Long non-coding RNAs (LncRNAs) have been linked to chemoresistance in many cancers. However, the function of lncRNA urothelial carcinoma associated1 (UCA1) in paclitaxel (PTX) resistance of OC is not well elucidated. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of UCA1, microRNA-654-5p (miR-654-5p) and salt inducible kinase 2 (SIK2). Cell PTX resistance and proliferation were evaluated by 3-(4, 5-dimethyl-2 thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay. The abilities of apoptosis, migration and invasion were measured by Flow cytometry and Transwell assays, respectively. Dual-luciferase reporter assay was used to verify the interaction among UCA1, miR-654-5p and SIK2. Besides, Western blot analysis was performed to assess the protein level of SIK2. UCA1 was markedly upregulated in OC tissues and PTX-resistant OC cells. Silencing of UCA1 restrained the PTX resistance, reduced the proliferation, migration, invasion and enhanced the apoptosis of PTX-resistant OC cells. MiR-654-5p could be sponged by UCA1, and the inhibitory effect of its overexpression on the progression of PTX-resistant OC cells could be reversed by overexpressed-UCA1. Moreover, SIK2 was a target of miR-654-5p. Silencing of SIK2 could hinder the PTX resistance and suppress the progression of PTX-resistant OC cells, while miR-654-5p inhibitor could invert this inhibitory effect. Also, the expression of SIK2 was regulated by miR-654-5p and UCA1 expression. LncRNA UCA1 plays an active role in PTX resistance of OC and is crucial to maintain the development of PTX resistance in OC, which provides a new therapeutic target for the study of OC chemoresistance.

LncRNA Urothelial Carcinoma-Associated 1 (UCA1) Regulates Rat Bone Marrow Mesenchymal Stem Cell Differentiation and Promotes Repair of Bone Defects

Bone marrow mesenchymal stem cells (BMSCs) have characteristics of self-renewal and multidirectional differentiation. LncRNA UCA1 regulates BMSCs differentiation. Whether LncRNA UCA1 plays a role in bone defects remains unclear. BMSCs were randomly divided into control group, radiation group (6Gy), radiation + UCA1 group followed by analysis of the expression of LncRNA UCA1, RUNX2 and OPN by real time PCR, BMSCs proliferation by MTT assay as well as ALP activity. Healthy Sprague-Dawley rats were randomly divided into control group; bone defect group; UCA1 group, in which UCA1-transfected BMSCs were infused into bone defect rats followed by analysis of bone mineral density, ALP activity as well as the formation of type II collagen by ELISA. LncRNA UCA1 expression was significantly decreased in BMSCs of irradiated group, with decreased BMSCs proliferation, reduced expression of RUNX2 and OPN as well as decreased ALP activity (P &lt; 0.05). Transfection of UCA1 significantly up-regulated LncRNA UCA1 expression in BMSCs, promoted BMSCs proliferation, increased the expression of RUNX2 and OPN, and the activity of ALP (P &lt; 0.05). In addition, UCA1 promoted bone mineral density, increased ALP activity and type II collagen formation in rats with bone defect. LncRNA UCA1 promotes osteogenic differentiation of BMSCs, and targeting it might be a novel approach to promote bone remodeling at the bone defect site.

RETRACTED: lncRNA UCA1 Promotes Gefitinib Resistance as a ceRNA to Target FOSL2 by Sponging miR-143 in Non-small Cell Lung Cancer

Exosomes could mediate cell-cell crosstalk in cancer progression by transferring long noncoding RNAs (lncRNAs). The aim of this study is to explore the roles of the exosomal lncRNA urothelial carcinoma-associated 1 (UCA1) on gefitinib resistance in non-small cell lung cancer (NSCLC). First, we detected the expression of UCA1 in gefitinib-resistant and gefitinib-sensitive NSCLC by quantitative real-time PCR; the expression occurred in tissues, cell lines, and exosomes. Cell phenotypes and animal experiments were performed to determine the effects of UCA1 and exosomal UCA1. Furthermore, bioinformatics online programs and luciferase reporter assay were used to validate the association of UCA1 and miR-143 in NSCLC cells. We observed that UCA1 was increased in both gefitinib-resistant NSCLC cells and their secreted exosomes. In vitro and in vivo experiments demonstrated that UCA1 knockdown impaired cell proliferation and promoted the gefitinib-induced cell apoptosis. Then we demonstrated that repressed UCA1 promoted the miR-143 expression, and miR-143 could bind to the predicted binding site of UCA1. We then dissected the effect of miR-143 on gefitinib resistance in NSCLC and proved the suppressive role of miR-143. Furthermore, we found that miR-143 displayed its role via modulating the FOSL2 expression. In summary, our findings indicate that exosomal UCA1 may serve as a promising therapeutic target for the treatment of epidermal growth factor receptor-positive (EGFR+) NSCLC patients.