Lung Cancer-associated Transcript Research Articles

Systematic analysis and characterization of long non-coding RNA genes in inflammatory bowel disease.

The cases of inflammatory bowel disease (IBD) are increasing rapidly around the world. Due to the multifactorial causes of IBD, there is an urgent need to understand the pathogenesis of IBD. As such, the usage of high-throughput techniques to profile genetic mutations, microbiome environments, transcriptome and proteome (e.g. lipidome) is increasing to understand the molecular changes associated with IBD, including two major etiologies of IBD: Crohn disease (CD) and ulcerative colitis (UC). In the case of transcriptome data, RNA sequencing (RNA-seq) technique is used frequently. However, only protein-coding genes are analyzed, leaving behind all other RNAs, including non-coding RNAs (ncRNAs) to be unexplored. Among these ncRNAs, long non-coding RNAs (lncRNAs) may hold keys to understand the pathogenesis of IBD as lncRNAs are expressed in a cell/tissue-specific manner and dysregulated in a disease, such as IBD. However, it is rare that RNA-seq data are analyzed for lncRNAs. To fill this gap in knowledge, we re-analyzed RNA-seq data of CD and UC patients compared with the healthy donors to dissect the expression profiles of lncRNA genes. As inflammation plays key roles in the pathogenesis of IBD, we conducted loss-of-function experiments to provide functional data of IBD-specific lncRNA, lung cancer associated transcript 1 (LUCAT1), in an in vitro model of macrophage polarization. To further facilitate the lncRNA research in IBD, we built a web database, IBDB (https://ibd-db.shinyapps.io/IBDB/), to provide a one-stop-shop for expression profiling of protein-coding and lncRNA genes in IBD patients compared with healthy donors.

Characterization of a Novel LUCAT1/miR-4316/VEGF-A Axis in Metastasis and Glycolysis of Lung Adenocarcinoma.

Objective: Accumulating literatures suggested that long non-coding RNAs (lncRNAs) were involved in tumorigenesis and cancer progression in lung adenocarcinoma (LUAD). However, the precise regulatory mechanism of lncRNA Lung cancer-associated transcript 1 (LUCAT1) in LUAD is not well defined. In this study, we aimed to investigate the biological function and mechanism of lncRNA LUCAT1 in regulating tumor migration and glycolysis of LUAD. Methods: High throughput sequencing was performed to identify differentially expressed lncRNAs between LUAD patients and healthy controls. The expression levels of LUCAT1 in LUAD clinical specimens or cell lines were evaluated by In situ hybridization (ISH) and quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). Functional experiments, including wound-healing, transwell invasion assays, glucose absorption, lactate metabolism and tumor xenograft experiments were conducted to identify the biological functions of LUCAT1 in LUAD. Silencing of LUCAT1, over-expression of LUCAT1 and miR-4316 were generated in LUAD cell lines to verify the regulatory mode of LUCAT1-mir-4316-VEGFA axis. Results: Our findings revealed that lncRNA LUCAT1 was significantly up-regulated in LUAD serum exosomes, tumor tissues, and LUAD cells in comparison with corresponding controls. Receiver operating characteristic curve (ROC) analysis indicated that the area under the curve (AUC) value of serum exosomal LUCAT1 reached 0.852 in distinguishing LUAD patients from healthy individuals. High expression of LUCAT1 in LUAD patient tissues was associated with enhanced Lymph Node Metastasis (LNM), advanced Tumor Node Metastasis (TNM) stage and poorer clinical outcome in LUAD patients. Knockdown of LUCAT1 inhibited LUAD cell metastasis and glycolysis in vitro as well as tumor metastasis in vivo, while overexpression of LUCAT1 induced a promoted LUAD metastasis and glycolysis. Furthermore, mechanistic investigations revealed that LUCAT1 elevated LUAD cell metastasis and glycolysis by sponging miR-4316, which further led to the upregulation of VEGFA. Finally, the regulatory axis LUCAT1-miR-4316-VEGFA was verified in LUAD. Conclusion: Our present research suggested that LUCAT1 facilitate LUAD cell metastasis and glycolysis via serving as a competing endogenous RNA to regulate miR-4316/VEGFA axis, which provided a novel diagnostic marker and therapeutic target for LUAD patients.

Long noncoding RNA LUCAT1 enhances the survival and therapeutic effects of mesenchymal stromal cells post-myocardial infarction

Mesenchymal stromal cell (MSC) transplantation has been a promising therapeutic strategy for repairing heart tissues post-myocardial infarction (MI). Nevertheless, its therapeutic efficacy remains low, which is mainly ascribed to the low viability of transplanted MSCs. Recently, long noncoding RNAs (lncRNAs) have been reported to participate in diverse physiological and pathological processes, but little is known about their role in MSC survival. Using unbiased transcriptome profiling of hypoxia-preconditioned MSCs (HP-MSCs) and normoxic MSCs (N-MSCs), we identified a lncRNA named lung cancer-associated transcript 1 (LUCAT1) under hypoxia. LUCAT1 knockdown reduced the survival of engrafted MSCs and decreased the MSC-based therapeutic potency, as shown by impaired cardiac function, reduced cardiomyocyte survival, and increased fibrosis post-MI. Conversely, LUCAT1 overexpression had the opposite results. Mechanistically, LUCAT1 bound with and recruited jumonji domain-containing 6 (JMJD6) to the promoter of forkhead box Q1 (FOXQ1), which demethylated FOXQ1 at H4R3me2(s) and H3R2me2(a), thus downregulating Bax expression and upregulating Bcl-2 expression to attenuate MSC apoptosis. Therefore, our findings revealed the protective effects of LUCAT1 on MSC apoptosis and demonstrated that the LUCAT1-mediated JMJD6-FOXQ1 pathway might represent a novel target to potentiate the therapeutic effect of MSC-based therapy for ischemic cardiovascular diseases.

Genome-wide differential expression profiling of lncRNAs and mRNAs in human induced pluripotent stem cell-derived endothelial cells exposed to e-cigarette extract

BackgroundElectronic-cigarette (e-cig) usage, particularly in the youth population, is a growing concern. It is known that e-cig causes endothelial dysfunction, which is a risk factor for the development of cardiovascular diseases; however, the mechanisms involved remain unclear. We hypothesized that long noncoding RNAs (lncRNAs) may play a role in e-cig-induced endothelial dysfunction.MethodsHere, we identified lncRNAs that are dysregulated in human induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) following 24 h of e-cig aerosol extract treatment via microarray analysis. We performed Gene Ontology and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analyses of the dysregulated mRNAs following e-cig exposure and constructed co-expression networks of the top 5 upregulated lncRNAs and the top 5 downregulated lncRNAs and the mRNAs that are correlated with them. Furthermore, the functional effects of knocking down lncRNA lung cancer-associated transcript 1 (LUCAT1) on EC phenotypes were determined as it was one of the significantly upregulated lncRNAs following e-cig exposure based on our profiling.Results183 lncRNAs and 132 mRNAs were found to be upregulated, whereas 297 lncRNAs and 413 mRNAs were found to be downregulated after e-cig exposure. We also observed that e-cig caused dysregulation of endothelial metabolism resulting in increased FAO activity, higher mitochondrial membrane potential, and decreased glucose uptake and glycolysis. These results suggest that e-cig alters EC metabolism by increasing FAO to compensate for energy deficiency in ECs. Finally, the knockdown of LUCAT1 prevented e-cig-induced EC dysfunction by maintaining vascular barrier, reducing reactive oxygen species level, and increasing migration capacity.ConclusionThis study identifies an expression profile of differentially expressed lncRNAs and several potential regulators and pathways in ECs exposed to e-cig, which provide insights into the regulation of lncRNAs and mRNAs and the role of lncRNA and mRNA networks in ECs associated e-cig exposure.

Long non-coding RNA LUCAT1 promotes the progression of clear cell renal cell carcinoma via the microRNA-375/YAP1 axis.

Clear cell renal cell carcinoma (ccRCC) is a common renal cell carcinoma with a high mortality rate. Lung cancer-associated transcript 1 (LUCAT1) has been reported to be a potential biomarker of prognosis in human ccRCC. However, the underlying mechanism of the function of LUCAT1 in ccRCC remains poorly understood. The present study aimed to investigate the role and underlying mechanism of LUCAT1 in ccRCC. The expression level of LUCAT1, microRNA-375 (miR-375) and yes-associated protein 1 (YAP1) in ccRCC tissues and cells was detected by reverse transcription-quantitative PCR, and the protein level of YAP1 was detected by western blotting. The effects of LUCAT1 on cell proliferation, migration and invasion were analyzed using Cell Counting Kit-8 and Transwell assays. The association between miR-375 and LUCAT1 or miR-375 and YAP1 was predicted by lncBase Predicted v.2 or TargetScan and verified using dual-luciferase reporter assay. The effect of LUCAT1 on ccRCC progression in vivo was evaluated using a xenograft tumor model. The results revealed that LUCAT1 and YAP1 were upregulated and miR-375 was downregulated in ccRCC tissues and cells. LUCAT1 knockdown suppressed cell proliferation, migration and invasion, which were reversed by the inhibition of miR-375. In addition, YAP1 overexpression attenuated the inhibitory effects of miR-375 overexpression on cell proliferation, migration and invasion. Subsequent experiments suggested that LUCAT1 regulated YAP1 expression by sponging miR-375. Therefore, LUCAT1 exerted its role by regulating the miR-375/YAP1 axis in vitro. Moreover, LUCAT1 knockdown suppressed the growth of ccRCC xenograft tumors in vivo. These results collectively revealed that LUCAT1 promoted the proliferation, migration and invasion of ccRCC by the upregulation of YAP1 via sponging miR-375, which may be used as a potential therapeutic target for ccRCC.

Lung cancer‑associated transcript 1 facilitates tumorigenesis in laryngeal squamous cell carcinoma through the targeted inhibition of miR‑493.

Long non-coding RNAs (lncRNAs) serve important roles in the tumorigenesis of a diverse range of cancer types. The lung cancer-associated transcript 1 (LUCAT1), has been reported to promote the proliferation, migration and invasion of oral squamous cell carcinoma cells. However, the exact role of LUCAT1 in laryngeal squamous cell carcinoma (LSCC) remains to fully understood. The present study aimed to interrogate the role and modulatory mechanism of LUCAT1 in LSCC. Reverse transcription-quantitative PCR and western blotting were used to investigate the expression of LUCAT1 and miR-493, as well as the protein expression of cyclin-dependent kinase 2, cyclin E1, p21, matrix metalloproteinase (MMP)2, MMP9, vascular endothelial growth factor-C, Bcl-2, Bax, cleaved caspase-3 and procaspase-3. Cell Counting Kit-8, flow cytometry, wound healing and Transwell assays were performed to analyze the proliferation, cell cycle, apoptosis levels, and the migratory and invasive abilities, respectively, of the LSCC AMC-HN-8 cell line. In addition, dual-luciferase reporter and ribonucleoprotein immunoprecipitation assays were used to investigate the binding between LUCAT1 and microRNA (miR)-493. The results of the present study revealed that the expression levels of LUCAT1 were upregulated in AMC-HN-8 cells. The genetic knockdown of LUCAT1 expression levels significantly suppressed the cell proliferation, alongside downregulating the expression levels of CDK2 and cyclin E1 and upregulating p21 expression levels. In addition, the knockdown of LUCAT1 inhibited cell migration and invasion, as demonstrated using the wound healing and Transwell assays, respectively. Moreover, LUCAT1 knockdown promoted cell apoptosis and upregulated the expression levels of Bax and cleaved caspase-3, whilst downregulating the expression levels of Bcl-2. Furthermore, LUCAT1 was discovered to directly bind to and inhibit the well-known tumor suppressor, miR-493. Notably, the specific inhibition of miR-493 partly blocked the anticancer effects of LUCAT1 knockdown in AMC-HN-8 cells. In conclusion, these results suggested that LUCAT1 may facilitate tumorigenesis in LSCC through the targeted inhibition of miR-493, which provides evidence for a novel target for the treatment of LSCC.

Downregulation of Long Noncoding RNA LUCAT1 Suppresses the Migration and Invasion of Bladder Cancer by Targeting miR-181c-5p.

Purpose The long noncoding RNA LUCAT1 (lung cancer-associated transcript 1) has been reported to be highly expressed in bladder cancer samples, but its role and molecular mechanisms need to be elucidated. Methods Bioinformatics methods show that miR-181c-5p is a target of LUCAT1. Here, we aimed to reveal whether LUCAT1 participates in the development of bladder cancer via targeting miR-181c-5p. The expression levels of LUCAT1 and miR-181c-5p were detected by RT-PCR technology in bladder cells and tissues. The effects of the LUCAT1/miR-181c-5p axis on cell proliferation, migration, invasion, and apoptosis were tested by CCK-8, wound healing, Transwell chambers, and flow cytometry assays. The expressions of apoptosis/migration-related proteins were detected by western blotting assays. Results The results demonstrated that LUCAT1 was overexpressed in bladder cancer tissue and cells, while miR-181c-5p showed a low expression pattern as compared to normal bladder cells and tissues. Cell proliferation, migration, and invasion capacities were significantly impaired, and cell apoptosis was enhanced when LUCAT1 was silenced in UM-UC-3 and T24 cell lines, but this effect was abolished by miR-181c-5p downregulation. In addition, miR-181c-5p downregulation impaired LUCAT1 downregulation which mediated the decreased expressions of Bcl2 and N-cadherin and the increased expressions of Bax and E-cadherin. Moreover, we found that KRAS was a direct target of miR-181c-5p and was under the positive regulation of LUCAT1. Conclusion Collectively, this study reveals that knockdown of LUCAT1 inhibits the migration and invasion of bladder cancer cells in a miR-181c-5p-dependent manner, which may be related to KRAS downregulation.

Serum LUCAT1 implicates the pathogenesis of muscle-invasive bladder cancer via targeting miR-199a-5p and miR-199b-5p.

Muscle-invasive bladder cancer (MIBC) is a common malignancy of urinary system cancers, accounting for about 1/3 of all newly diagnosed bladder cancer cases. Due to its strong metastasis, the 5-year survival of MIBC is less than 50%, and in serious cases, the overall survival of metastatic bladder cancer patients is about 1.3years. LncRNAs, a type of non-coding RNAs defined as the transcripts exceeding 200 nucleotides in length, are frequently aberrant in multiple cancers including cervical, ovarian, breast and bladder cancers. Recently, LUCAT1 (short for lung cancer-associated transcript 1), a lncRNA first reported to be involved in smoking-related lung cancer, has been observed to exhibit crucial roles in the epithelial-to-mesenchymal transition (EMT), migration and invasion processes of clear cell renal cell carcinoma (ccRCC) and colorectal cancer. However, whether it involves in the pathogenesis of MIBC remains underexplored. In the present study, LUCAT1 was up-regulated in the serum samples of MIBC patients and bladder cancer cell lines, as assessed using real-time PCR. Our in vitro data (including wound healing and trans-well assays) showed that LUCAT1 was required for the proliferation, EMT, migration and invasion processes of T24 cells. Moreover, LUCAT1 directly targeted miR-199a-5p and miR-199b-5p, as affirmed using the luciferase reporter assay, and manipulation of LUCAT1 significantly suppressed miR-199a-5p and miR-199b-5p. Collectively, our findings highlight an axis of LUCAT1/miR-199a/b-5p in MIBC pathogenesis. Therefore, LUCAT1 may possibly be a promising candidate for diagnostic biomarker and therapeutic target of MIBC.

Long non‑coding RNA LUCAT1 contributes to cisplatin resistance by regulating the miR‑514a‑3p/ULK1 axis in human non‑small cell lung cancer.

Drug resistance is a major obstacle in the therapy of malignant tumors, including non-small cell lung cancer (NSCLC). Long non-coding RNAs (lncRNAs) have been demonstrated to be involved in chemoresistance. The present study aimed to investigate the role of lung cancer-associated transcript 1 (LUCAT1) in cisplatin (DDP) resistance in NSCLC. By using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), it was found that the expression of LUCAT1 was elevated and that of microRNA-514a-3p (miR-514a-3p) was decreased in DDP-resistant NSCLC tissues and cells. Functionally, LUCAT1 upregulation enhanced cisplatin resistance by promoting the viability, autophagy and metastasis, and inhibiting the apoptosis of NSCLC cells, as demonstrated by Cell Counting kit-8 (CCK-8) assay, western blot analysis, Transwell assay and flow cytometric analysis. LUCAT1 was identified as a sponge of miR-514a-3p and uncoordinated-51-like kinase 1 (ULK1) was proven to be a target gene of miR-514a-3p by bioinformatics analysis, dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. The enhancing effect of miR-514a-3p on cisplatin sensitivity was reversed by the elevation of LUCAT1. ULK1 knockdown suppressed cisplatin resistance, while this effect was attenuated by miR-514a-3p inhibition. Moreover, LUCAT1 positively regulated ULK1 expression by targeting miR-514a-3p. In addition, LUCAT1 knockdown suppressed tumor growth in vivo. On the whole, the findings of the present study demonstrate that LUCAT1 contributes to the resistance of NSCLC cells to cisplatin by regulating the miR-514a-3p/ULK1 axis, elucidating a novel regulatory network in cisplatin resistance in NSCLC.

WITHDRAWN: Long non-coding RNA LUCAT1 up-regulates the expression of HIF-1α and promotes the proliferation and metastasis of breast cancer cells via sponging miR-199a-5p

Abstract Background Long non-coding RNA (lncRNA) lung cancer associated transcript 1 (LUCAT1) plays an important regulatory role in a variety of cancers, but its role in breast cancer is still unclear. Methods Quantitative real-time polymerase chain reaction (qRT-PCR) was used to investigate the expression of LUCAT1, miR-199a-5p, HIF-1α in breast cancer tissues and cell lines; CCK8 method was used to detect the proliferation of breast cancer cells; Transwell assay was adopted to evaluate the migration and invasion of breast cancer cells; luciferase reporter gene assay was used to validate the interaction between LUCAT1 and miR-199a-5p. Western blot was utilized to analyze the effects of LUCAT1 and miR-199a-5p on the expression of HIF-1α. Results LUCAT1 was significantly up-regulated in breast cancer and cell lines; overexpression of LUCAT1 promoted the proliferation, migration and invasion of breast cancer cells. Additionally, LUCAT1 functioned as “ceRNA” to modulate the expression of miR-199a-5p, in turn regulated the expression of HIF-1α. Conclusion LUCAT1 is an oncogenic lncRNA in breast cancer, and it can inhibit the function of miR-199a-5p and increase the expression of HIF-1α, promoting the proliferation, migration and invasion of cancer cells.

LncRNA LUCAT1 promotes proliferation of ovarian cancer cells by regulating miR-199a-5p expression.

To investigate the biological effect of long non-coding ribonucleic acid (lncRNA) lung cancer-associated transcript 1 (LUCAT1) in the development of ovarian cancer. Real-time quantitative polymerase chain reaction (RT-qPCR) was utilized to detect the expression levels of lncRNA LUCAT1 in three human ovarian cancer cell lines (CaoV-3, SK-OV-3 and HO-8910) and the normal human ovarian surface epithelial cell line (IOSE80). Small interfering RNAs against lncRNA LUCAT1 (si-LUCAT1) were transfected into SK-OV-3 cells. Transfection efficiency of si-LUCAT1 was verified via RT-qPCR. Cell Counting Kit-8 (CCK-8) and colony formation assays were performed to test the effect of silencing lncRNA LUCAT1 on SK-OV-3 cell proliferation. The apoptosis was measured by flow cytometry. The miRcode database was searched to predict potential microRNAs (miRNAs) binding lncRNA LUCAT1. It was found that lncRNA LUCAT1 contained a highly conserved binding site of miR-199a-5p in the 3'-untranslated region (3'-UTR). Subsequently, the targeting relationship between them was determined through Dual-Luciferase reporter gene assay and RT-qPCR analysis. LncRNA LUCAT1 was highly expressed in three human ovarian cancer cell lines compared to that in normal ovarian surface epithelial cell line (p<0.05). The cell proliferation rate in SK-OV-3 cells with lncRNA LUCAT1 knockdown was remarkably lower in comparison to that in control group. Moreover, colony formation assay also revealed that the number of cell clones decreased significantly after knockdown of lncRNA LUCAT1 compared to that in control group (p<0.05). In addition, the apoptosis rate was distinctly elevated in the lncRNA LUCAT1 silencing group (p<0.05). Furthermore, a highly conserved binding site of miR-199a-5p was found in the 3'-UTR of lncRNA LUCAT1. Dual-Luciferase reporter gene assay exhibited that the Luciferase activity of LUCAT1-wt was significantly reduced after overexpression of miR-199a-5p (p<0.05), while that of LUCAT1-mut was unchangeable. Further analysis via RT-qPCR suggested that miR-199a-5p overexpression significantly decreased the expression level of lncRNA LUCAT1 (p<0.05). LncRNA LUCAT1 is overexpressed in ovarian cancer cells, which may target miR-199a-5p to exert its effects on driving the malignant development of ovarian cancer.

LUCAT1 Epigenetically Downregulates the Tumor Suppressor Genes CXXC4 and SFRP2 in Gastric Cancer.

PurposeThe mechanisms of Wnt/β-catenin pathway signaling and abnormal expression of tumor suppressor genes is not well known in gastric cancer (GC). Long non-coding RNA (lncRNA) has recently been identified as a possible link therein. In this study, we investigated the role of lung cancer associated transcript 1 (LUCAT1) in GC.Materials and MethodsThe expression of LUCAT1 in GC cell lines and 100 tissue samples was examined by qRT-PCR. Two different siRNAs were used for knockdown of LUCAT1 expression. Cell viability was assessed by MTT assay. To analyze metastasis, scratch wound-healing assay, a Matrigel invasion assay, and colony formation assay were performed. Apoptosis was analyzed by PI/Annexin-V staining. To check the methylation status in tumor suppressor genes, methylation-specific PCR was carried out. Western blot was performed to detect epithelial-mesenchymal transition and apoptosis markers upon silencing of LUCAT1 (siLUCAT1).ResultsLUCAT1 expression in GC cell lines and tissues was significantly elevated, compared to that in normal gastric cells and adjacent non-tumor tissues (p<0.001). Two different siRNAs for LUCAT1 reduced cell proliferation, invasion, and migration, compared to siCT (p<0.05), and these reductions were restored by pcDNA-LUCAT1 (p<0.05). siLUCAT1 elicited upregulation of the expression of CXXC4 and SFRP2. The expression of H3K27me3 was reduced by siLUCAT1, and this reduction was correlated with methylation of CXXC4 and SFRP2. Inhibition of LUCAT1 up-regulated EZH2 expression and resulted in demethylation of CXXC4 and SFRP2 through the Wnt/β-catenin signaling pathway.ConclusionWe concluded that LUCAT1 induces methylation of CXXC4 and SFRP2, thereby regulating Wnt/β-catenin signaling in GC.

Long Noncoding RNA LUCAT1 Promotes Multiple Myeloma Cell Growth by Regulating the TGF-β Signaling Pathway.

Objective:Long noncoding RNAs (lncRNAs) are potential biomarkers for cancers. Nevertheless, the ability of long noncoding RNA lung cancer-associated transcript 1 in patients with multiple myeloma remains unknown. The purpose of this current study was to figure out its function in multiple myeloma.Methods:Firstly, the expression of long noncoding RNA lung cancer-associated transcript 1 in cancer or normal tissues and serum from patients with multiple myeloma and normal donors was detected. Secondly, the expression of long noncoding RNA lung cancer-associated transcript 1 was overexpressed or silenced in U266 and H929 cells, respectively to detect changes of proliferation and apoptosis in multiple myeloma in vitro. Subsequently, the expression of transforming growth factor-β signaling pathway-related proteins was detected by western blot analysis. Finally, the effect of long noncoding RNA lung cancer-associated transcript 1 on the growth of multiple myeloma cells in vivo was evaluated by tumor xenograft in nude mice.Results:Long noncoding RNA lung cancer-associated transcript 1 was increased in cancer tissues and serum of patients with multiple myeloma as well as multiple myeloma cells, which was correlated with dismal prognosis of patients with multiple myeloma. Overexpression of long noncoding RNA lung cancer-associated transcript 1 promoted the activity of U266 and H929 cells, while inhibition of long noncoding RNA lung cancer-associated transcript 1 suppressed the activity of U266 and H929 cells. In addition, long noncoding RNA lung cancer-associated transcript 1 was found to promote activation of the transforming growth factor-β signaling pathway. Furthermore, long noncoding RNA lung cancer-associated transcript 1 knockdown restricted the growth of multiple myeloma cells in vivo.Conclusion:This study suggests that suppression of long noncoding RNA lung cancer-associated transcript 1 inhibits the activation of transforming growth factor-β signaling pathway, thereby inhibiting the growth of multiple myeloma cells.

Clinical Value of lncRNA LUCAT1 Expression in Liver Cancer and its Potential Pathways.

Emerging studies indicate that long noncoding RNAs (lncRNAs) play a role as prognostic markers in many cancers, including liver cancer. Here, we focused on the lncRNA lung cancer-associated transcript 1 (LUCAT1) for liver cancer prognosis. RNA-seq and phenotype data were downloaded from the Cancer Genome Atlas (TCGA). Chisquare tests were used to evaluate the correlations between LUCAT1 expression and clinical features. Survival analysis and Cox regression analysis were used to compare different LUCAT1 expression groups (optimal cutoff value determined by ROC). The log-rank test was used to calculate the p-value of the Kaplan-Meier curves. A ROC curve was used to evaluate the diagnostic value. Gene Set Enrichment Analysis (GSEA) was performed, and competing endogenous RNA (ceRNA) networks were constructed to explore the potential mechanism. Data mining of the TCGA -Liver Hepatocellular Carcinoma (LIHC) RNA-seq data of 371 patients showed the overexpression of LUCAT1 in cancerous tissue. High LUCAT1 expression was associated with age (p=0.007), histologic grade (p=0.009), T classification (p=0.022), and survival status (p=0.002). High LUCAT1 patients had a poorer overall survival and relapse-free survival than low LUCAT1 patients. Multivariate analysis identified LUCAT1 as an independent risk factor for poor survival. The ROC curve indicated modest diagnostic performance. GSEA revealed the related signaling pathways, and the ceRNA network uncovered the underlying mechanism. High LUCAT1 expression is an independent prognostic factor for liver cancer.

LncRNA LUCAT1 contributes to cell proliferation and migration in human pancreatic ductal adenocarcinoma via sponging miR-539.

Pancreatic ductal adenocarcinoma is one of the most aggressive and dreadful malignancies worldwide. Long noncoding RNAs (lncRNAs) have emerged as vital regulators in the development of human malignancies and other disorders. This study aimed to characterize the role of lncRNA lung cancer‐associated transcript 1 (lncRNA LUCAT1), a novel cancer‐related lncRNA, in human PDAC. Here we initially analyzed the expression patterns of lncRNA LUCAT1 and evaluated its clinical significance. The qRT‐PCR analysis and in situ hybridization staining showed that lncRNA LUCAT1 expression was significantly increased in tumorous tissues compared with adjacent normal tissues. Additionally, we found that increased lncRNA LUCAT1 expression was linked to larger tumor size and lymphatic invasion. Consistently, lncRNA LUCAT1 was remarkably up‐regulated in PDAC cell lines. To better understand the biological role of lncRNA LUCAT1, we evaluated the effects of lncRNA LUCAT1 knockdown on PDAC cell proliferation, cell cycle progression, migration, and invasion using MTT assays, flow cytometry, Transwell migration, and invasion assays, respectively. Functional studies demonstrated that lncRNA LUCAT1 knockdown dramatically suppressed PDAC cell proliferation, induced cell cycle arrest and inhibited cell migration and invasion. Tumor xenograft in vivo assays displayed that lncRNA LUCAT1 inhibited tumorigenecity of PDAC cells. Mechanistic studies uncovered that lncRNA LUCAT1 acted as a molecular sponge of miR‐539 and that miR‐539 mediated the effects of lncRNA LUCAT1 on PDAC cell proliferation, cell cycle progression, and motility. Collectively, our findings may offer some novel insights into understanding lncRNA LUCAT1 in PDAC.

LncRNA LUCAT1 facilitates tumorigenesis and metastasis of triple-negative breast cancer through modulating miR-5702

Triple-negative breast cancer (TNBC) is a subtype of aggressive breast cancer with high recurrence and poor survival. Emerging evidence has indicated that long non-coding RNAs (lncRNAs) play pivotal roles in the development and progression of multiple cancers. Although there are substantial studies revealing that lung cancer-associated transcript 1 (LUCAT1) functions as a tumor promotor in various human cancers, the molecular mechanism of LUCAT1 in TNBC remains largely to be explored. In our study, we identified that LUCAT1 expression was dramatically enhanced in TNBC samples and cells. High LUCAT1 expression was strongly associated with advanced stages and poor prognosis of TNBC. LUCAT1 contributed to TNBC development through accelerating cell proliferation, cell cycle progression and metastasis as well as attenuating cell apoptosis. Moreover, miR-5702 was proved to directly bind to LUCAT1 and be negatively modulated by LUCAT1. Knockdown of miR-5702 reversed the suppressing influences of LUCAT1 depletion on TNBC progression. In conclusion, it was the first investigation to shed light on the significant function and underlying regulatory mechanism of LUCAT1 in TNBC tumorigenesis. We validated that LUCAT1 induced tumorigenesis and metastasis of TNBC via miR-5702, which provided clues for improving the treatment of TNBC.

LncRNA SCAL1 inhibits inducible nitric oxide synthase in lung cells under high-glucose conditions.

The lungs are one of the most common target organs of diabetic injury in patients with diabetes. Long non-coding RNA (lncRNA) smoke and cancer-associated lncRNA 1 (SCAL1), also known as lung cancer associated transcript 1 (LUCAT1), is known to have a pivotal role in lung cancer. The aim of the current study was to investigate the potential involvement of SCAL1 in diabetic lung disease. The expression levels of SCAL1 were determined by reverse transcription-quantitative PCR in serum samples from healthy controls (n=40), diabetic patients without lung disease (n=56) and diabetic patients with diabetic lung disease (n=44). Receiver operating characteristic analysis was used to evaluate the diagnostic value of serum SCAL1 in discriminating diabetic patients with diabetic lung disease from diabetic patients without lung disease and healthy controls. Pearson's correlation analysis was performed to examine the correlation between SCAL1 and inducible nitric oxide synthase (iNOS) mRNA expression levels in blood and lung tissue samples. Expression levels of iNOS and NO production following treatment with high (30 mM) glucose were examined by western blot analysis and NO assay, respectively. The expression levels of SCAL1 were significantly downregulated in diabetic patients with diabetic lung disease, and downregulated serum expression levels of SCAL1 effectively distinguished diabetic patients with diabetic lung disease from diabetic patients without lung disease and healthy controls. Treatment with high glucose significantly upregulated SCAL1 expression in normal lung cells. Furthermore, the overexpression of SCAL1 inhibited iNOS protein expression and reduced NO production in cells treated with high glucose. In conclusion, the current study demonstrated that lncRNA SCAL1 inhibits iNOS protein expression in lung cells under high-glucose conditions, which suggests that SCAL1 may have potential in the treatment of patients with diabetic lung disease.

Long non-coding RNA LINP1 induces tumorigenesis of Wilms' tumor by affecting Wnt/β-catenin signaling pathway.

Recent studies have discovered that long non-coding RNAs (lncRNAs) play an important role in the development of malignant tumors. The aim of this work was to investigate the exact role of lncRNA LINP1 in the development of Wilms' tumor and to explore the possible underlying mechanism. The expression of lncRNA in non-homologous end joining pathway 1 (LINP1) in tissue samples of Wilms' tumor was detected by Real Time-quantitative Polymerase Chain Reaction (RT-qPCR). The relationship between the expression of lung cancer associated transcript 1 (LUCAT1) and patients' overall survival time was analyzed. Subsequent functional experiments were conducted to identify the changes in biological behaviors of Wilms' tumor cells after the gain or loss of LINP1. Moreover, the underlying mechanism of LINP1 function was explored. QRT-PCR results showed that LINP1 expression level in Wilms' tumor tissues was significantly higher than that of adjacent tissues. LINP1 expression was negatively associated with the overall survival time of patients with Wilms' tumor. Cell growth ability was markedly inhibited and promoted after down-regulation and overexpression of LINP1 in vitro, respectively. Moreover, after the loss and gain of LINP1 in vitro, cell migration and invasion abilities were remarkably repressed and promoted, respectively. Furthermore, the loss of LINP1 in vitro could significantly decrease the expressions of targeted proteins in the Wnt/β-catenin signaling pathway. However, the expressions of targeted proteins in the Wnt/β-catenin signaling pathway were remarkably up-regulated after over-expression of LINP1. LINP1 could enhance cell metastasis and proliferation via inducing the Wnt/β-catenin signaling pathway. Our findings might provide a new prospect for the diagnosis and therapy of Wilms' tumor.

SP1-induced up-regulation of lncRNA LUCAT1 promotes proliferation, migration and invasion of cervical cancer by sponging miR-181a

Long noncoding RNA lung cancer associated transcript 1 (LUCAT1) has been shown to be a lncRNA that facilitates the development and progression of several tumours. However, the evidence of LUCAT1 modulating the growth and metastasis of cervical cancer (CC) were still lacking. The present study aimed to explore the expression pattern, biological function and potential mechanism of LUCAT1 in CC. In this study, we, first, confirmed that LUCAT1 acted as an up-regulated lncRNA by analyzing the data from GCTA dataset and RT-PCR in both CC tissues and cell lines. We also showed that TINCR overexpression is induced by nuclear transcription factor SP1. Then, clinical assays showed that LUCAT1 was associated with advanced clinical progression and poor prognosis of CC patients. Importantly, multivariate Cox model confirmed that LUCAT1 expression was an independent prognostic factor for both 5-year overall survival in CC. Then, lost-function assays revealed that knockdown of LUCAT1 significantly suppressed CC cells proliferation, colony formation, migration, invasion and EMT by a series of cells experiments. Mechanistically, Bioinformatic tools predicted that miR-181a may target LUCAT1, which was confirmed using luciferase reporter assay and RNA immunoprecipitation (RIP) assays. Overall, our findings showed that SP1-activated LUCAT1 exerts an oncogenic function in CC by binding to miR-181a, suggesting that miR-181a may be a ponderable and promising therapeutic target for CC.

Long non-coding RNA LUCAT1 promotes tumourigenesis by inhibiting ANXA2 phosphorylation in hepatocellular carcinoma.

Long non‐coding RNAs (lncRNAs) play essential roles in diverse biological processes; however, current understanding of the mechanism underlying the regulation of tumour proliferation and metastasis is limited. Lung cancer‐associated transcript 1 (LUCAT1) has been reported in a variety of human cancers, while its role in hepatocellular carcinoma (HCC) remains unclear. This study aimed to determine the biological role and underlying mechanism of LUCAT1 on progression and metastasis in HCC cells and clinical specimens. Our results demonstrated that LUCAT1 was up‐regulated in HCC tissues and cells. Loss‐ and gain‐of‐function studies revealed that LUCAT1 promotes the proliferation and metastasis of HCC cells in vitro and in vivo. Furthermore, RNA pulldown and Western blot assays indicated that LUCAT1 inhibited the phosphorylation of Annexin A2 (ANXA2) to reduce the degradation of ANXA2‐S100A10 heterotetramer (AIIt), which in turn accelerated the secretion of plasminogen into plasmin, thereby resulting in the activation of metalloprotease proteins. In conclusion, we propose that LUCAT1 serves as a novel diagnostic and therapeutic target for HCC.