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.

Dysregulation of Serum UCA1 and Its Clinical Significance in Patients with Acute Cerebral Infarction.

OBJECTIVE: To investigate the expression of lncRNA UCA1 in serum of patients with acute cerebral infarction (ACI) and its relationship with prognosis. METHODS: The serum lncRNA UCA1 level in participants was detected, and the correlation between the neurological function score (NIHSS score) of ACI patients and lncRNA UCA1 expression was analyzed. Patients were followed up at 3 months after discharge and were divided into favorable and unfavorable prognostic groups according to the modified Rankin scale (mRs). The risk factors of ACI patients with poor prognosis were analyzed, and the predictive value of each index for ACI prognosis was evaluated by ROC curve. RESULTS: The level of lncRNA UCA1 in ACI group was increased (P<0.001). ROC analysis showed that high lncRNA UCA1 expression had clinical significance for the diagnosis of ACI. Spearman correlation analysis revealed that NIHSS score was positively correlated with lncRNA UCA1 expression level in ACI group (r=0.6537, P<0.001). Hcy level and NIHSS score in poor prognosis group (n=63) were higher than those in good prognosis group (n=84), and lncRNA UCA1 level in serum in poor prognosis group was increased in comparison to good prognosis group (P<0.05). Logistic regression analysis investigated that admission NIHSS score, infarct size, and increased lncRNA UCA1 were the risk factors affecting the prognosis of ACI. CONCLUSION: Serum lncRNA UCA1 is abnormally elevated in ACI patients, and the elevated lncRNA UCA1 not only shows high accuracy in the diagnosis of ACI, but also has a certain predictive value for poor prognosis of ACI.

lncRNA UCA1 regulates miR-132/Lrrfip1 axis to promote vascular smooth muscle cell proliferation.

UCA1 is predicted to bind to miR-132, which is a key player in the proliferation of vascular smooth muscle cells (VSMCs). This research studied the role of lncRNA UCA1 in atherosclerosis. The binding of UCA1 to miR-132 was proved by dual luciferase activity assay and RNA immunoprecipitation. UCA1 and miR-132 failed to affect each other's expression in VSMCs. UCA1 was upregulated and miR-132 was decreased in atherosclerosis plasma. However, they are not closely correlated across atherosclerosis and control plasma sample. Interestingly, UCA1 suppressed the role of miR-132 in downregulating Lrrfip1 expression and promoting VSMC proliferation. Therefore, UCA1 is downregulated in atherosclerosis and may regulate miR-132/Lrrfip1 axis to promote VSMC proliferation.

Low level TGF-ß1-treated Umbilical mesenchymal stem cells attenuates microgliosis and neuropathic pain in chronic constriction injury by exosomes/lncRNA UCA1／miR-96-5p／FOXO3a.

Neuropathic pain is a chronic pain state that usually caused by injuries in peripheral or central nerve. Inhibition of spinal microglial response is a promising treatment of neuropathic pain caused by peripheral nerve injury. In recent years, mesenchymal stem cells (MSCs) that characterized with multipotent ability have been widely studied for disease treatment. TGF-ß1 is a well-known regulatory cytokine that participate in the response to cell stress and is closely correlated with the function of nerve system as well as MSC differentiation. This work aimed to determine the effects of exosomes that extracted from TGF-ß1-induced umbilical mesenchymal stem cells (hUCSMCs) on the neuropathic pain. In this work, we established a rat model of chronic constriction injury (CCI) of the sciatic nerve and LPS-induced microglia cell model. The hUCSMCs cell surface biomarker was identified by flow cytometry. Exosomes that extracted from TGF-ß1-treated hUCSMCs were characterized by transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA) and used for treatment. We observed that TGF-ß1 upregulates the level of lncRNA UCA1 (UCA1) in hUCMSC-derived exosomes. Treatment with exosomal lncRNA UCA1 (UCA1) alleviated the neuropathic pain, microgliosis, and production of inflammatory mediator both in vivo and in vitro. UCA1 directly interact with the miR-96-5p, and the miR-96-5p acts as sponge of FOXO3a. Knockdown of UCA1 upregulated the level of miR-96-5p and downregulated the FOXO3a expression, which could be recovered by inhibition of miR-96-5p. In summary, the TGF-ß1-stimulated exosomal UCA1 from hUCMSCs alleviates the neuropathic pain and microgliosis. These findings may provide novel evidence for treatment of neuropathic pain caused by chronic constriction injury.

The Functional Role of LncRNA UCA1 in Pancreatic Cancer: a mini-review.

Pancreatic cancer (PaC) is a common malignant tumor of the digestive tract, with a 5-year survival rate of less than 5% and high mortality rate in the world. LncRNAs have been showed to possess multiple biological functions in growth, differentiation, and proliferation, which play an important role in different biological processes and diseases, especially in the development of tumors. LncRNA UCA1, which is firstly identified in human bladder cancer, has been showed to be a tumor promoter in pancreatic cancer. Recent researches have showed that UCA1 might promote pancreatic carcinogenesis and progression, and correlate with drug resistance. In this review, we address the biological function and regulatory mechanism of UCA1 in pancreatic cancer, which might give a new approach for clinical diagnosis and treatment.

lncRNA UCA1 inhibits mitochondrial dysfunction of skeletal muscle in type 2 diabetes mellitus by sequestering miR-143-3p to release FGF21.

Increasing evidence suggests that insulin resistance in type 2 diabetes mellitus (T2DM) is associated with mitochondrial dysfunction in skeletal muscle, while the underlying molecular mechanisms remain elusive. This study aims to construct a ceRNA regulatory network that is involved in mitochondrial dysfunction of skeletal muscle in T2DM. Based on GEO database analysis, differentially expressed lncRNA and mRNA profiles were identified in skeletal muscle tissues of T2DM. Next, LASSO regression analysis was conducted to predict the key lncRNAs related to T2DM, which was validated by receiver operating characteristic (ROC) analysis. Moreover, the miRNAs related to skeletal muscle in T2DM were identified by WGCNA, followed by construction of gene-gene interaction network and GO and KEGG enrichment analyses. It was found that 12 lncRNAs and 6 miRNAs were related to skeletal muscle in T2DM. Moreover, the lncRNA-miRNA-mRNA ceRNA network involving UCA1, miR-143-3p, and FGF21 was constructed. UCA1, and FGF21 were downregulated, while miR-143-3p was upregulated in skeletal muscle cells (SkMCs) exposed to palmitic acid. Additionally, ectopic expression experiments were performed in SkMCs to confirm the effects of UCA1/miR-143-3p/FGF21 on mitochondrial dysfunction by determining mitochondrial ROS, oxygen consumption rate (OCR), membrane potential, and ATP level. Overexpression of miR-143-3p increased ROS accumulation and reduced the OCR, fluorescence ratio of JC-1, and ATP level, which were reversed by upregulation of UCA1 or FGF21. Collectively, lncRNA UCA1 inhibited mitochondrial dysfunction of skeletal muscle in T2DM by sequestering miR-143-3p away from FGF21, therefore providing a potential therapeutic target for alleviating mitochondrial dysfunction of skeletal muscle in T2DM.

N-nitrosamines-mediated downregulation of LncRNA-UCA1 induces carcinogenesis of esophageal squamous by regulating the alternative splicing of FGFR2.

Concerns are raised over the risk to digestive system's tumors from the N-nitrosamines (NAs) exposure in drinking water. Albeit considerable studies are conducted to explore the underlying mechanism responsible for NAs-induced esophageal squamous cell carcinoma (ESCC), the exact molecular mechanisms remain largely unknown, especially at the epigenetic regulation level. In this study, it is revealed that the urinary concentration of N-Nitrosodiethylamine is higher in high incidence area of ESCC, and the lncRNA-UCA1(UCA1) is significantly decreased in ESCC tissues. In vitro and in vivo experiments further show that UCA1 is involved in the malignant transformation of Het-1A cells and precancerous lesions of the rat esophagus induced by N-nitrosomethylbenzylamine (NMBzA). Functional gain and loss experiments verify UCA1 can affect the proliferation, migration, and invasion of ESCC cells in vitro and in vivo. Mechanically, through binding to heterogeneous nuclear ribonucleoprotein F (hnRNP F) protein, UCA1 regulates alternative splicing of fibroblast growth factor receptor 2 (FGFR2), which promotes the FGFR2IIIb isoform switching to FGFR2 IIIc isoform, and the latter activates epithelial-mesenchymal transition via PI3K-AKT signaling pathways impacting tumorigenesis. Therefore, NAs-mediated downregulation of UCA1 promotes ESCC progression through targeting hnRNP F/FGFR2/PI3k-AKT axis, which provides a new chemical carcinogenic target and establishes a previously unknown mechanism for NAs-induced ESCC.

Evaluation of the Regulatory Role of Circadian Rhythm Related Long Non-Coding RNAs in ADHD Etiogenesis.

OBJECTIVE: ADHD is associated with increased sleep problems and circadian rhythm disturbances. This study aimed to examine ADHD patients and healthy controls in terms of chronotypic features and expression levels of CLOCK, PER1, lncRNA HULC, lncRNA UCA1. METHOD: Eighty-three children were included (43 ADHD). Conner's Parent Rating Scale-Revised Short Form, Childhood Chronotype Questionnaire, Children's Sleep Disorders Scale were administered. Gene expression levels were studied from peripheral blood. RESULTS: Evening chronotype, sleep initiation/maintenance disorder, sleep-wake transition disorder, excessive sleepiness disorder were higher in the ADHD group compared to the controls in the scales reported by the parents. Expression levels of all examined genes were statistically significantly higher in the ADHD group. There was no significant relationship between genes and sleep parameters in the ADHD group. CONCLUSION: Our study provides the first evidence that lncRNA HULC and lncRNA UCA1 might have a role in the etiology of ADHD.

Silencing of UCA1 attenuates the ox-LDL-induced injury of human umbilical vein endothelial cells via miR-873-5p/MAPK8 axis.

LncRNA UCA1 plays a vital role in cardiovascular diseases. Endothelial cell dysfunction is a prerequisite for atherosclerosis (AS) development. However, the pathophysiological role of UCA1 in endothelial cell dysfunction induced by ox-LDL remains obscure. Here, we observed that UCA1 was upregulated in the sera of patients with AS and ox-LDL-treated endothelial cells. UCA1 knockdown dramatically reduced the cell apoptosis induced by ox-LDL and the production of pro-inflammatory cytokines and ROS in endothelial cells. Mechanistically, we found that UCA1 directly targeted miR-873-5p. UCA1 knockdown increased, while UCA1 overexpression decreased the expression of miR-873-5p. Further, we found that mitogen-activated protein kinase 8 (MAPK8) was a downstream target gene of miR-873-5p. MAPK8 overexpression or miR-873-5p knockdown reduced the enhancement of ox-LDL-induced cell apoptosis, oxidative stress, and pro-inflammatory cytokine production conferred by UCA1 knockdown. In conclusion, UCA1 can protect Human Umbilical Vein Endothelial Cells from ox-LDL-induced injury via the miR-873-5p/MAPK8 axis.

LncRNA-UCA1 regulates lung adenocarcinoma progression through competitive binding to miR-383.

The present study aimed to assess the role of the long non-coding RNA-urothelial cancer associated 1 (lncRNA-UCA1)/microRNA (miR)-383/vascular endothelial growth factor A (VEGFA) axis in regulating lung adenocarcinoma physiology through in vivo and in vitro experiments. The expression profile of lncRNA-UCA1 was analyzed by genome-wide analysis from GSE146459. The cell counting Kit-8, colony formation, wound healing and transwell assays were performed to evaluate the effects of lncRNA-UCA1 in vitro. In addition, luciferase reporter assays were performed to confirm the binding site. The expression levels of miR-383 and VEGFA in tumor cells were measured using reverse transcription-quantitative PCR. HCC-78 was also transfected with miR-383 mimics, inhibitors and siRNA-VEGFA before their viability was also assessed. Xenograft models were established in nude mice to investigate the tumor characteristics in vivo. The expression of lncRNA-UCA1 was significantly increased in tumor tissues and cells compared with adjacent tissues or HBE cells. Silencing lncRNA-UCA1 expression in cells resulted in a reduction in lung cancer cell viability. In addition, lncRNA-UCA1 silencing increased the expression of miR-383. Inhibiting miR-383 expression increased HCC-78 proliferation, migration and invasion, whilst reducing their apoptosis. miR-383 was shown to specifically target VEGFA to inhibit its expression at both the protein and mRNA levels. VEGFA knockdown resulted in a reduction in all aforementioned aspects of HCC-78 cell activity. In addition, inhibiting miR-383 expression led to larger tumor sizes in vivo. To conclude, the results of the study suggest that lncRNA-UCA1 can regulate the expression of miR-383 and, in turn, VEGFA.

Long noncoding RNA urothelial carcinoma associated 1 protects human placental vascular endothelial cells from hypoxia-induced damage by regulating the miR-197-3p/histone deacetylase-2 axis in patients with pregnancy-induced hypertension.

PURPOSE: Pregnancy-induced hypertension (PIH) is a major cause of mortality among pregnant women, fetuses, and newborns. This study assessed the role of long noncoding RNA (lncRNA) urothelial carcinoma associated 1 (UCA1) in PIH development. METHODS: Serum samples were collected from 30 pregnant women with PIH and 30 healthy pregnant women. Serum UCA1, miR-197-3p, and histone deacetylase-2 (HDAC2) mRNA level was evaluated using quantitative polymerase chain reaction. The expression of UCA1, miR-197-3p and HDAC2 in human placental vascular endothelial cells (HPVECs) was regulated by transfection. HPVECs were treated with hypoxia reoxygenation (H/R) to establish the PIH cell model. Methyl thiazolyl tetrazolium (MTT) assay, the terminal transferase uridyl nick end labelling (Tunel) assay and tubule formation assay were performed to assess the viability, apoptosis and angiogenesis of HPVECs. Dual-luciferase reporter gene assay, RNA pull-down assay, and RNA immunoprecipitation assay were performed to identify the binding between two genes. Western blot analysis was used for protein expression detection. RESULTS: In pregnant women with PIH, serum UCA1 and HDAC2 expression was downregulated and serum miR-197-3p expression was upregulated. H/R induction decreased the viability and angiogenesis of HPVECs, and increased the apoptosis of HPVECs. In H/R-induced HPVECs, UCA1 upregulation increased the viability and angiogenesis, and decreased the apoptosis. Downregulation of UCA1 had a contrasting result. UCA1 competitively binds to miR-197-3p to upregulate the expression of HDAC2. HDAC2 knockdown counteracted the effect of UCA1 upregulation on the viability, apoptosis and angiogenesis of HPVECs. CONCLUSIONS: LncRNA UCA1 protected HPVECs from hypoxia-induced damage by regulating the miR-197-3p/HDAC2 axis in PIH.

LncRNA UCA1 accelerates osteosarcoma progression via miR-145 and Wnt/ß-catenin pathway.

Long non-coding (lnc) urothelial cancer associated 1 (UCA1) has been confirmed to participate in osteosarcoma (OS), but its specific mechanism is still under investigation. The study was designed to reveal the interaction between UCA1 and its downstream effector molecules, so as to determine whether there is any interaction of regulating physiological processes in tumor cells. Here, we studied the signaling cascade involving UCA1, miR-145, and HMGA1. The expression of UCA1 and miR-145 levels was interfered to assess their effects on physiological processes of tumor cells. The relationship between UCA1 and miR-145 as well as between HMGA1 and miR-145 was identified by the dual-luciferase reporter (DLR) assay, and the in vivo effect of UCA1 was estimated in nude mouse xenografts. As a result, a negative association was found between UCA1 and miR-145 in OS cells. Both UCA1 knockout and miR-145 over-expression inhibited malignant progression and induced apoptosis in MG-63 and U2OS cells. UCA1 knockout led to an increase in miR-145 and decreases in HMGA1, p-ß-catenin and cyclin D1. In addition, UCA1 upregulation promoted tumor growth in vitro and changed miR-145 and HMGA1 levels in vivo. Moreover, the DLR assay and RNA immunoprecipitation (RIP) showed that UCA1 was likely to regulate HMGA1 levels by sponging miR-145. Overall, the inhibition of UCA1 increases miR-145 levels and decreases HMGA1 levels, thereby exerting an anti-tumor role in OS.

lncRNA UCA1 induces autophagic gene expression via epigenetic regulation mediated by ATG16L1 and miR-132-3p in SH-SY5Y cells treated with retinoic acid

Objective: Epilepsy is a chronic brain disease with recurrent seizures. Autophagy plays a crucial role in the progression of epilepsy. This study aimed to explore the function and intrinsic mechanism of the long non-coding RNA (lncRNA) UCA1/miR-132-3p/ATG16L1 axis in epilepsy via regulation of autophagy. Methods: The expression of lncRNA UCA1, miR-132-3p and ATG16L1 was measured in serum from epileptic patients by quantitative RT-PCR. A SH-SY5Y cell model was further constructed using retinoic acid to investigate the UCA1/ miR-132-3p/ATG16L1 axis by quantitative RT-PCR, western blotting, fluorescence in situ hybridisation, RNA immunoprecipitation, chromatin immunoprecipitation, and a dual-luciferase reporter gene assay. Results: In the serum of epileptic patients, the level of lncRNA UCA1 and ATG16L1 was reduced and miR-132-3p elevated, compared to controls. Similarly, in the SH-SY5Y cell model, the level of lncRNA UCA1 and ATG16L1 was reduced and miR-132-3p elevated in retinoic acid-treated cells; lncRNA UCA1 was mainly located in the cytoplasm. lncRNA UCA1 overexpression was shown to promote autophagic gene expression, which was reversed by miR-132-3p overexpression. Moreover, autophagic gene expression induced by miR-132-3p knockdown was reversed by ATG16L1 knockdown. Based on precipitation assays, lncRNA UCA1 and miR-132-3p were shown to form a complex with the transcription factor, EZH2, and miR-132-3p was shown to interact with ATG16L1 based on a luciferase assay. Finally, lncRNA UCA1 was shown to negatively regulate miR-132-3p expression, and miR-132-3p was shown to negatively regulate ATG16L1. Significance: In this cell model, lncRNA UCA1 promotes autophagic gene expression via epigenetic regulation mediated by ATG16L1 and miR-132-3p.

Long Non-coding RNA UCA1 Regulates SRPK1 Expression Through miR- 99b-3p in Ovarian Cancer.

BACKGROUND: Ovarian carcinoma (OC) is one of the most common malignancies of the female reproductive organs, with a low survival rate primarily due to the lack of effective methods for early diagnosis and prognosis. OBJECTIVE: In this article, our motivation is to explore the lncRNA-related network mechanisms involved in the pathogenesis of OC. METHODS: Public lncRNAs and mRNA expression datasets for OC were collected from the Gene Expression Omnibus (GEO) database. By integrated bioinformatics analysis, we constructed a UCA1-miRNA-mRNA network. We studied lncRNA-related molecular modulation mechanism in ovarian cancer cells based on MTT assay, dual luciferase reporter gene assays, quantitative realtime PCR, and western blotting. RESULTS: UCA1 was higher in ovarian tumor tissues and cells than normal tissues and cells. It was demonstrated in this study that knockdown of UCA1 inhibited ovarian cancer cell viability, which a miR-99b-3p inhibitor could reverse in vitro. Further, UCA1 was shown to regulate the expression of SRPK1 by directly binding to miR-99b-3p. CONCLUSION: These results suggest that UCA1 functions as an oncogene in ovarian cancer. Inhibition of UCA1/miR-99b-3p/SRPK1 axis may become a novel target for treating ovarian cancer.

Involvement of blood lncRNA UCA1 in sepsis development and prognosis, and its correlation with multiple inflammatory cytokines.

BACKGROUND: Sepsis is a highly life-threatening disease. Long non-coding RNA urothelial carcinoma associated 1 (lncRNA UCA1) participates in the processes of inflammation and organ injury in several diseases, whereas its role in sepsis patients is still unclear. The aim was to explore the clinical value of lncRNA UCA1 in sepsis patients. METHODS: One hundred seventy-four sepsis patients and 100 age and gender-matched controls were enrolled. LncRNA UCA1 in peripheral blood mononuclear cell samples was examined, and the level of inflammatory cytokines in serum samples was assessed. RESULTS: LncRNA UCA1 was highly expressed in sepsis patients compared with controls. LncRNA UCA1 was positively correlated with tumor necrosis factor-α, interleukin (IL)-6, IL-17, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1 in sepsis patients, while it was not correlated with these inflammatory cytokines in controls. lncRNA UCA1 upregulation was related to raised APACHE II score and SOFA score in sepsis patients. Moreover, lncRNA UCA1 was increased in sepsis deaths compared with sepsis survivors and was independently correlated with increased 28-day sepsis mortality risk. Further receiver operating characteristic curves presented that lncRNA UCA1 had a good value to predict 28-motality risk, while its combination with other independent factors (including age, history of chronic kidney disease, G+ bacterial infection, Fungus infection, C-reactive protein, and APACHE II score) exerted a great predictive value for 28-day mortality risk. CONCLUSION: LncRNA UCA1 is upregulated and correlates with multiple pro-inflammatory cytokines, terrible disease severity, and poor prognosis in sepsis patients.

Up-regulation of LncRNA UCA1 by TGF-ß promotes doxorubicin resistance in breast cancer cells.

BACKGROUND: Doxorubicin (DOX) resistance remains a major challenge for adriamycin-based treatment of breast cancer (BC). Transforming growth factor ß (TGF-ß) has been reported to contribute to drug resistance. Although the role of long noncoding RNAs (LncRNAs) in cancer progression has been widely studied, its effect on TGF-ß-induced resistance remains limited. This study aimed to investigate the role of LncRNA on the regulation of TGF-ß-induced drug resistance. METHODS: Cell counting kit-8 (CCK-8) and an EdU assay were used to evaluate cell viability and proliferation. The level of LncRNA mRNA expression in BC tissues and cells was examined by quantitative real-time PCR. Changes in epithelial-mesenchymal transition (EMT) and cell apoptosis were quantified by Western blot and immunofluorescence. RESULTS: TGF-ß induced EMT and promoted DOX resistance. LncRNA urothelial carcinoma-associated 1(lncRNA UCA1) associated with TGF-ß was upregulated in BC cells and tissues. LncRNA UCA1 silencing enhanced sensitivity to DOX decreased cellular proliferation and increased apoptosis in BC cells. The effect of TGF-ß on EMT and DOX resistance disappeared following a lncRNA UCA1 knockdown. CONCLUSIONS: These findings suggest that lncRNA-UCA1, a mediator of TGF-ß signaling, could predispose BC patients to EMT and DOX resistance.

LncRNA UCA1 regulates silicosis-related lung epithelial cell-to-mesenchymal transition through competitive adsorption of miR-204-5p.

The main clinical manifestations are pulmonary fibrosis, silicosis, is one of the most common types of pneumoconiosis, and its pathogenesis is still unclear. The proliferation and transdifferentiation of fibroblasts are considered to be the key link leading to pulmonary fibrosis. Type II alveolar epithelial cells can be transformed into lung fibroblasts through epithelial-mesenchymal transition (EMT) to promote lung fibrosis. Involved in the EMT process of a variety of cancers, lncRNA UCA1 (UCA1) has been shown to competitively adsorb miR-204-5p, and play an effect on the downstream target gene E-box binding zinc finger protein 1 (ZEB1), thereby promoting EMT to facilitate the invasion and migration of cancer cells. This is an important potential intervention target that affects the process of EMT, but it has not been reported in the study of EMT related to silicosis. Therefore, this study established a SiO2 dust-treated mouse silicosis model and an in vitro EMT model of A549 cells to observe the changes and effects of UCA1 and miR-204-5p, and intervene on the two respectively. The results showed that the EMT process existed in the aforementioned models, while UCA1 was upregulated in the in vitro model. Double luciferase reporter assay demonstrated the targeted binding of UCA1 and miR-204-5p. Silencing UCA1 can up-regulate the expression of miR-204-5p and reduce the level of ZEB1, thus inhibiting EMT process, while intervention of miR-204-5p can change the level of ZEB1 and regulate EMT. Therefore, UCA1 may release its target gene ZEB1 through competitive adsorption of miR-204-5p to regulate EMT process.

LncRNA UCA1/miR-182-5p/MGMT axis modulates glioma cell sensitivity to temozolomide through MGMT-related DNA damage pathways.

Glioblastoma (GBM) is the most malignant subtype of gliomas. GBM resistance to temozolomide (TMZ) remains a huge challenge. O6-methylguanine-DNA methyltransferase (MGMT) is mainly responsible for repairing DNA alkylation damage caused by alkylating drugs such as TMZ; therefore, it has been regarded as the major cause of the resistance to TMZ. Hematoxylin and eosin (H&E) and immunohistochemical (IHC) staining were performed in tissue sections. LncRNA urothelial cancer-associated 1 (UCA1) knockdown was conducted via the transfection of the plasmid containing small interfering RNA (siRNA) targeting lncRNA UCA1. Cell viability and apoptosis were examined using MTT assay and flow cytometry. Nude mouse tumorigenicity assay was performed to detect tumor formation in vivo. MGMT expression and lncRNA UCA1 expression were increased in high-grade glioma tissues and cells. UCA1 knockdown in glioma cells enhanced TMZ efficacies in affecting glioma cell viability, cell apoptosis, MGMT protein level, and DNA damage markers in vitro, as well as tumorigenesis in vivo. Moreover, miR-182-5p targeted UCA1 and MGMT; miR-182-5p inhibited MGMT expression. Similar to UCA1 knockdown, miR-182-5p overexpression also promoted TMZ effects on glioma cell phenotype, MGMT expression level, and the levels of DNA damage markers. Under TMZ treatment, the efficacies of UCA1 knockdown in MGMT expression level and glioma cell sensitivity to TMZ were notably reversed after miR-182-5p overexpression. Taken together, we demonstrate the lncRNA UCA1/miR-182-5p/MGMT axis modulates glioma cell sensitivity to TMZ via MGMT-related DNA damage pathways.

Long noncoding RNA UCA1 promotes glutamine-driven anaplerosis of bladder cancer by interacting with hnRNP I/L to upregulate GPT2 expression.

Long noncoding RNA urothelial cancer associated 1 (UCA1), initially identified in bladder cancer, is associated with multiple cellular processes, including metabolic reprogramming. However, its characteristics in the anaplerosis context of bladder cancer (BLCA) remain elusive. We identified UCA1 as a binding partner of heterogeneous nuclear ribonucleoproteins (hnRNPs) I and L, RNA-binding proteins (RBPs) with no previously known role in metabolic reprogramming. UCA1 and hnRNP I/L profoundly affected glycolysis, TCA cycle, glutaminolysis, and proliferation of BLCA. Importantly, UCA1 specifically bound to and facilitated the combination of hnRNP I/L to the promoter of glutamic pyruvate transaminase 2 (GPT2), an enzyme transferring glutamate to α-ketoglutarate, resulting in upregulated expression of GPT2 and enhanced glutamine-derived carbons in the TCA cycle. We also systematically confirmed the influence of UCA1 and hnRNP I/L on metabolism and proliferation via glutamine-driven anaplerosis in BLCA. Our study revealed the critical role of UCA1-mediated mechanisms involved in glutamine-driven anaplerosis and provided novel evidence that lncRNA regulates metabolic reprogramming in tumor cells.

The possibility of early diagnosis of colorectal cancer through expression of Lncrna UCA1, Lncrna LINC00970, and Wnt genes; an in-vitro study

Colorectal cancer is the 4thcause of cancer death; with considering the growth process of this cancer and the necessity of early diagnosis, the purpose of the research is to state the LncRNA 00970, LncRNA UCAI,and the Wntgene before and after the treatment by 5-Azacytidine epigenetic medicine, to reach the biomarker in the very first steps of colorectal cancer. In this experiment, the human colon cancer cell line (HT29) treated with different concentrations of 5-aza-2'-deoxycytidine (5-aza-dC) was utilized to induce DNA demethylation; Quantitative PCR (qPCR) was used to measure LncRNA UCA1and LncRNA LINC00970 and Wntexpression. There was a significant relationship between the expression of LncRNA 00970, LncRNA UCAI,and the Wntgene and its effects on colorectal (p < 0.05). The Wntgene was treated by 1 and 10 of 5-Azacytidine epigenetic medicine, which then experienced decreases. In LncRNA UCAI and LncRNA00970 in dose 1 micromolar of 5-Azacytidine had decrement and increment of expressionrespectively that explains their efficiency but in treatment by dose 10 mM of this medicine, no significant LncRNA expression difference was detected, 5-azacitidine has a direct impact on its target genes and LncRNAs.Therefore, it can be used in the early diagnosis of colorectal cancer.