lncRNA DLEU1 Research Articles

GPR37-centered ceRNA network contributes to metastatic potential in lung adenocarcinoma: Evidence from high-throughput sequencing

The competing endogenous RNA (ceRNA)-based profiling has been extensively studied in carcinogenesis of lung adenocarcinoma (LUAD), while it has seldomly been applied to investigate the metastatic potential of LUAD. This study aims to examine the function and in-depth mechanism of GPR37-centered ceRNA network in LUAD. Cancer tissues and adjacent normal tissues from three LUAD patients were collected for high-throughput sequencing to screen for differentially expressed genes. A PPI network was constructed to screen the key gene GPR37, followed by analysis for the functions and pathways. Clinical data from LUAD patients were integrated with gene expression data in TCGA-LUAD dataset for survival analysis. Based on the miRNAs targeting_GPR37 and lncRNAs targeting_miRNAs, a lncRNA-miRNA-mRNA ceRNA network was established. GPR37 was up-regulated in LUAD tissue samples, and it may be a key gene involved in LUAD progression. GPR37 in LUAD was mainly enriched in the mitosis-related pathways. High GPR37 expression corresponded to poor prognosis in LUAD patients. Meanwhile, GPR37 could be used as an independent factor to predict the prognosis in LUAD patients. LncRNA DLEU1, up-regulated in LUAD tissue samples, may competitively bind to miR-4458 to up-regulate the expression of the miR-4458 downstream target GPR37. DLEU1 was associated with poor prognosis and tumor metastasis in LUAD patients. Altogether, our findings reveal a novel ceRNA network of DLEU1/miR-4458/GPR37 in LUAD growth and metastasis.

LncRNA DLEU1 promotes angiogenesis in diabetic foot ulcer wound healing by regulating miR-96-5p.

Diabetic foot ulcer (DFU) carries high rates of major amputation and mortality. The goals of this study were to identify expression of circulating lncRNA DLEU1 and miR-96-5p in patients with diabetic foot ulcer (DFU) and to explore the function of lncRNA DLEU1/miR-96-5p axis in DFU. Matched patients with DFU and healthy individuals were randomly selected. Serum samples from all subjects were used for circulating lncRNA DLEU1 and miR-96-5p assessment by RT-qPCR. Receiver operating characteristic (ROC) curve was plotted to assess the discriminative capacity of lncRNA DLEU1 and miR-96-5p in identifying DFU. Cell proliferation was detected by CCK-8 assay. Cell apoptosis was assayed by Annexin V-FITC/PI staining method. Bioinformatics, luciferase reporter activity assay, and in vitro cell experiments were used to explore the relationship between lncRNA DLEU1 and miR-96-5p. LncRNA DLEU1 and miR-96-5p were significantly up- and downregulated in patients with DFU, respectively, compared with controls. After ROC assessment, lncRNA DLEU1 and miR-96-5p were found to discriminate DFU from miR-96-5p. Furthermore, lncRNA DLEU1 inhibited human umbilical vein endothelial cells (HUVECs) cell proliferation and increased HUVECs apoptosis and oxidative stress through sponging miR-96-5p. Our findings suggest lncRNA DLEU1 and miR-96-5p as circulating biomarkers for DFU. Also, we provide the clue for the pathogenic significance of lncRNA DLEU1/miR-96-5p in DFU, as well as insights for new potential targets.

Prognostic value and mechanism of long non-coding RNA DLEU1 in osteosarcoma

To investigate the prognostic value and mechanism of long non-coding RNA DLEU1(LncRNA DLEU1) in osteosarcoma. The tissue samples and clinical data of 86 patients with osteosarcoma treated by orthopaedic surgery in our hospital from January 2012 to December 2014 were retrospectively collected. The expression of LncRNA DLEU1 in pathological tissues was detected by qRT-PCR, then the patients were divided into high and low expression of LncRNA DLEU1 groups. Osteosarcoma cell line HOS was divided into two groups, down-regulated expression group (si-DLEU1 group) and negative control group (si-NC group). LncRNA DLEU1 siRNA and negative control sequence were transfected by Lipofectamine 3000. Chi-square test was used to analyze the relationship between the expression of LncRNA DLEU1 and the clinicopathological factors of osteosarcoma. Kaplan-Meier method was used to compare the difference of the overall survival rate of osteosarcoma patients between the high and low expression groups of LncRNA DLEU1. The risk factors affecting the overall survival rate of osteosarcoma were analyzed by single factor and multifactor analysis. The number of invasive cells in the two groups was determined and compared by Transwell assay. The expression of LncRNA DLEU1 in osteosarcoma tissue was higher than that in adjacent tissues (P<0.001). The expression of LncRNA DLEU1 in human osteosarcoma cell lines (MG-63, U-2 OS, and HOS) was significantly higher than that in human osteoblast line hFOB 1.19 (P<0.001). The expression of LncRNA DLEU1 was significantly correlated with Enneking stage (P<0.001), distant metastasis (P=0.016), and histological grade (P=0.028). The 1-year overall survival rate of the LncRNA DLEU1 high expression group was significantly higher than that of the low expression group (90.7% vs 60.5%, P<0.001). The 5-year overall survival rate of the LncRNA DLEU1 high expression group was significantly higher than that of the low expression group (32.6% vs 11.6%, P<0.001). Univariate analysis showed that Enneking stage (P<0.001), tumor size (P=0.043), distant metastasis (P<0.001), histological grade (P<0.001), and expression of LncRNA DLEU1 (P<0.001) were risk factors for overall survival of osteosarcoma patients. Multivariate analysis showed that high expression of LncRNA DLEU1 [HR=1.948, 95% CI(1.141, 3.641), P=0.012] and distant metastasis[HR=4.108, 95% CI(2.169, 7.780), P<0.001] were independent risk factors for overall survival of osteosarcoma patients. The number of invasive cells in si-DLEU1 group was significantly lesser than that in si-NC group(139±13 vs 357±31, P<0.001). High expression of LncRNA DLEU1 is a molecular marker affecting the prognosis of osteosarcoma patients. Downregulation of LncRNA DLEU1 can inhibit the invasion of osteosarcoma cells.

Cancer associated fibroblasts suppressed ferroptosis in glioblastoma via upregulating lncRNA DLEU1.

Background: Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults. It is crucial to elucidate the mechanism underlying ferroptosis resistance in GBM. Methods: We used qRT-PCR to detect the level of DLEU1 and mRNAs of indicated genes, while protein levels were determined by western blots. FISH was applied to validate the sublocation of DLEU1 in GBM cells. Gene knockdown or overexpression was achieved by transient transfection. Ferroptosis markers were detected by indicated kits and TEM. RNA pull -down, RIP, CHIP-qPCR, and dual -luciferase assay were used to validate the direct interaction between indicated key molecules in the current study. Results: We validated that the expression of DLEU1 was upregulated in GBM samples. DLEU1 knockdown exacerbated erastin -induced ferroptosis in LN229 and U251MG cells, as well as in the xenograft model. Mechanistically, we found that DLEU1 bound with ZFP36 and facilitated ZFP36 to degrade ATF3 mRNA, thus upregulating the expression of SLC7A11 to attenuate erastin -induced ferroptosis. Importantly, our results confirmed that cancer-associated fibroblasts (CAF) conferred ferroptosis resistance in GBM. The stimulation of CAF conditioned medium enhanced the activation of HSF1, and HSF1 transcriptionally increased the level of DLEU1 to regulate erastin -induced ferroptosis. Conclusion: This study identified DLEU1 as an oncogenic lncRNA that epigenetically downregulates ATF3 expression via binding with ZFP36 to facilitate ferroptosis resistance in GBM. The upregulation of DLEU1 in GBM might be attributed to CAF -induced HSF1 activation. Our study might provide a research basis for understanding CAF -induced ferroptosis resistance in GBM.

LncRNA DLEU1 facilitates the progression of oral squamous cell carcinoma by miR-126-5p/GAB1 axis.

Oral squamous cell carcinoma (OSCC) is one of the most frequent malignancies found in head and neck cancers. Dysregulation of lncRNAs has been proposed to be related to the development of OSCC. Here, we investigated the function and probable mechanisms of lncRNA DLEU1 in OSCC. OSCC cell lines and human oral keratinocytes (HOKs) were cultured, while SCC-25 and CAL-27 cells were transfected with the corresponding plasmids. Reverse transcription quantitative PCR (RT-qPCR) and western blot were carried out to measure the RNA and protein levels. Cell proliferation, migration and invasion were evaluated using MTT assays, wound healing and Transwell assays. The StarBase database predicted the interactions between DLEU1 and miR-126-5p, as well as miR-126-5p and GAB1, which were further validated using a dual-luciferase reporter assay. Our results indicated that DLEU1 and GAB1 were upregulated, while miR-126-5p was downregulated in OSCC cells. Silencing DLEU1 reduced OSCC cell proliferation, migration, and invasion, while DLEU1 overexpression had the opposite effects. DLEU1 mediated biological effects in OSCC through binding to miR-126-5p, which directly targeted GAB1. miR-126-5p knockdown rescued the inhibitory function of DLEU1 depletion on proliferation, migration and invasion. Meanwhile, the miR-126-5p mimic exerted suppressive functions in the progression of OSCC, which were neutralized after GAB1 overexpression. In summary, lncRNA DLEU1 targets the miR-126-5p/GAB1 axis to aggravate OSCC progression, providing a novel target for treating OSCC.

LncRNA DLEU1 Modulates Proliferation, Inflammation, and Extracellular Matrix Degradation of Chondrocytes through Regulating miR-671-5p.

Long noncoding RNAs (lncRNAs) have been shown to be involved in the development of osteoarthritis. However, the expression, function, and mechanism of DLEU1 in OA development remain largely unclear. The present reference demonstrates that DLEU1 is overexpressed in OA specimens compared to control cartilages. Inflammatory cytokines IL-1β, TNF-α, and IL-6 induce DLEU1 expression in chondrocytes. Ectopic expression of DLEU1 induces chondrocyte proliferation, degradation of ECM, and inflammation mediators such as IL-6, IL-8, and TNF-α secretion. Moreover, we demonstrated that DLEU1 targets miR-671-5p expression in chondrocytes. Overexpression of DLEU1 suppresses miR-671-5p expression in chondrocytes. The expression of miR-671-5p is decreased in OA specimens compared to control cartilages. There is a negative correlation between the expression of miR-671-5p and DLEU1 in OA specimens. Inflammatory mediators IL-1β, TNF-α, and IL-6 suppress miR-671-5p expression in OA specimens. Elevated expression of miR-671-5p suppresses chondrocyte proliferation, degradation of ECM, and secretion of inflammation mediators. DLEU1 overexpression promotes chondrocytes proliferation, degradation of ECM, and secretion of inflammation mediators via regulating miR-671-5p. These results suggested that DLEU1 acts as one destructive role in OA development via regulating miR-671-5p.

LncRNA DLEU1 is overexpressed in premature ovarian failure and sponges miR-146b-5p to increase granulosa cell apoptosis

BackgroundmiR-146b-5p has been reported to participate in premature ovarian failure (POF) in mice. However, its role in POF patients is unclear. We predicted that miR-146b-5p might interact with lncRNA DLEU1, a crucial player in ovarian cancer. We then explored the interaction between DLEU1 and miR-146b-5p.MethodsExpression of DLEU1 and miR-146b-5p in POF and control ovary tissues was determined by RT-qPCR. The subcellular location of DLEU1 in human KGN cells was analyzed using subcellular fractionation assays. The direct interaction between DLEU1 and miR-146b-5p was analyzed using RNA pull-down assays. The role of DLEU1 in miR-146a expression was analyzed using overexpression assay. Cell proliferation was analyzed using cell apoptosis assay.ResultsIncreased DLEU1 expression and decreased miR-146b-5p expression were observed in POF. DLEU1 directly interacted with MiR-146b-5p and was expressed in both nuclear and cytoplasm samples of KGN cells. In KGN cells, DLEU1 and miR-146b-5p failed to regulate the expression of each other. However, DLEU1 promoted cell apoptosis and reduced the inhibitory effects of miR-146b-5p on cell apoptosis.ConclusionsDLEU1 is overexpressed in POF and sponges miR-146b-5p to increase KGN cell apoptosis.

LncRNA DLEU1 Contributes to the Growth and Invasion of Colorectal Cancer via Targeting miR-320b/PRPS1.

Growing evidences suggest that long non-coding RNAs (lncRNAs) are closely correlated to the development of human cancer, such as colorectal cancer (CRC). A previous report suggested that DLEU1 accelerated CRC development. However, DLEU1’s underlying mechanism in CRC remains unclear. In our study, the level of DLEU1 in CRC tissues is investigated by qRT-PCR. Our data exhibited that DLEU1 level was observably increased in CRC tissues and CRC cell lines and was closely associated with bad prognosis of CRC patients. CRC cell proliferation was repressed by sh-LncRNA DLEU1, whereas cell apoptosis was markedly stimulated. Moreover, knockdown of DLEU1 inhibited cell migration and invasion. Mechanistically, through interacting with miR-320b in CRC, DLEU1 promoted the level of PRPS1 which was a target of miR-320b. The rescue experiment confirmed that knockdown of DLEU1 repressed cell proliferation, migration and invasion while stimulated cell apoptosis via miR-320b/phosphoribosyl pyrophosphate synthetase 1 (PRPS1) axis. Meanwhile, the data of xenograft model exhibited that inhibition of DLEU1 suppressed tumor growth in vivo. In summary, DLEU1 knockdown may repress PRPS1 expression via miR-320b, and then repress cell proliferation, migration and invasion while stimulate cell apoptosis. Our research may provide a novel target for the treatment of CRC.

Expression of LncRNA DLEU1 in Esophageal Squamous Cell Carcinoma and Its Effect on Proliferation and Migration of ESCC Cells

Expression of LncRNA DLEU1 in Esophageal Squamous Cell Carcinoma and Its Effect on Proliferation and Migration of ESCC Cells

Knockdown lncRNA DLEU1 Inhibits Gliomas Progression and Promotes Temozolomide Chemosensitivity by Regulating Autophagy.

Gliomas are the most fatal malignant cerebral tumors. Temozolomide (TMZ), as the primary chemotherapy drug, has been widely used in clinics. However, resistance of TMZ still remains to poor defined. LncRNAs have been reported to play crucial roles in progression of various cancers and resistance of multiple drugs. However, the biological function and underlying mechanisms of most lncRNAs in glioma still remains unclear. Based on the TCGA database, a total of 94 differentially expressed lncRNAs, including 16 up-regulated genes and 78 downregulated genes were identified between gliomas and normal brain tissues. Subsequently, lncRNA DLEU1, HOTAIR, and LOC00132111 were tested to be significantly related to overall survival (OS) between high- and low-expression groups. Additionally, we verified that lncRNA DLEU1 was high expressed in 108 gliomas, compared with 19 normal brain tissues. And high expression of lncRNA DLEU1 predicted a poor prognosis (HR = 1.703, 95%CI: 1.133–2.917, p-value = 0.0159). Moreover, functional assays revealed that knockdown of lncRNA DLEU1 could suppress the proliferation by inducing cell cycle arrest at G1 phase and reducing the S phase by down-regulating the CyclinD1 and p-AKT, as the well as migration and invasion by inhibiting the epithelial–mesenchymal transition (EMT) markers, such as ZEB1, N-cadherin, β-catenin and snail in glioma cells. Furthermore, silencing lncRNA DLEU1 suppressed TMZ-activated autophagy via regulating the expression of P62 and LC3, and promoted sensitivity of glioma cells to TMZ by triggering apoptosis. Conclusively, our study indicated that lncRNA DLEU1 might perform as a prognostic potential target and underlying therapeutic target for sensitivity of glioma to TMZ.

Silencing of lncRNA DLEU1 inhibits tumorigenesis of ovarian cancer via regulating miR-429/TFAP2A axis.

Long non-coding RNAs (lncRNAs) are known as crucial regulators in the development of OC. In the current study, we aim to explore the function and molecular mechanism of lncRNA DLEU1 in OC. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to determine the expression of DLEU1, miR-429, and TFAP2A in OC cells and tissues. The relationship among DLEU1, miR-429, and TFAP2A was tested by dual-luciferase reporter (DLR) assay. Besides, the proliferative, migratory and invasive abilities of OC cells were analyzed by MTT, wound healing, and transwell assays, respectively. Western blot was performed to determine the protein expression of TFAP2A. The expression of lncRNA DLEU1 and TFAP2A were upregulated, and miR-429 was downregulated in OC tissues. Silencing of DLEU1 inhibited the proliferation, migration, and invasion of OC cells. Bioinformation and DLR assay showed that DLEU1 acted as the sponge for miR-429. Moreover, miR-429 could directly target TFAP2A and inhibit the proliferation, migration, and invasion of OC cells. Moreover, we observed a negative correlation between miR-429 and DLEU1, and between miR-429 and TFAP2A in OC tissues. The transfection of miR-429 inhibitor or pcDNA-TFAP2A reversed the inhibitory effects of si-DLEU1 on the proliferation, migration, and invasion of OC cells. Silencing of DLEU1 inhibited the proliferation, migration, and invasion of OC cells by regulating miR-429/TFAP2A axis, indicating a potential therapeutic target for OC.

DLEU1: A Functional Long Noncoding RNA in Tumorigenesis.

LncRNA DLEU1 participates in various biological processes, playing an indispensable role in the pathophysiology of human diseases, especially in tumorigenesis and other processes. Besides, it may represent a promising target for biotherapy in numerous tumors. The aim of this review was to reveal the pathophysiological functions and mechanisms of lncRNA DLEU1 in different types of cancer. In this review, current studies concerning the biological functions and mechanisms of DLEU1 in tumor development are summarized and analyzed; the related researches are collected through a systematic retrieval of PubMed. DLEU1 is a novel cancer-associated lncRNA that has been proved to be abnormally elevated in various malignancies, containing osteosarcoma, glioma, glioblastoma multiforme, hepatocellular carcinoma, bladder cancer, cervical cancer, non-small cell lung cancer, pancreatic ductal adenocarcinoma, colorectal cancer, oral squamous cell carcinoma, endometrial cancer, gastric cancer, Burkitt lymphoma and ovarian carcinoma. Besides, lncRNA LDEU1 has been demonstrated involving in the procession of proliferation, migration, invasion and inhibition of apoptosis of cancer cells. Long non-coding RNA DLEU1 is likely to represent an available biomarker or a potential therapeutic target in multiple tumors.

HMGA1 promotes the development of esophageal squamous cell carcinoma by mediating miR-671-5p/lncRNA DLEU1.

HMGA1 promotes the development of esophageal squamous cell carcinoma by mediating miR-671-5p/lncRNA DLEU1.

LncRNA DLEU1 accelerates the malignant progression of clear cell renal cell carcinoma via regulating miRNA-194-5p.

The aim of this study was to illustrate the role of long non-coding RNA (lncRNA) DLEU1 in regulating the malignant progression of clear cell renal cell carcinoma (ccRCC) by targeting microRNA-194-5p (miRNA-194-5p). DLEU1 expression level in ccRCC tissues and para-cancerous tissues was determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The correlation between DLEU1 expression and pathological indexes of ccRCC patients was assessed. After the silence of DLUE1, the proliferative and migratory abilities of ACHN and 786-O cells were evaluated. Furthermore, Dual-Luciferase reporter gene assay and rescue experiments were conducted to identify the role of DLEU1/miRNA-194-5p in regulating the ccRCC progression in vitro. DLEU1 expression was markedly up-regulated in ccRCC tissues when compared with para-cancerous tissues. The rates of lymphatic metastasis and distant metastasis in ccRCC patients with a high level of DLEU1 were significantly higher, whereas the prognosis was significantly worse. Transfection of si-DLEU1 remarkably attenuated proliferative and migratory abilities of ACHN and 786-O cells. MiRNA-194-5p was identified as the target gene of DLEU1. In addition, the knockdown of miRNA-194-5p could reverse the regulatory effect of DLEU1 on the proliferative and metastatic abilities of ccRCC. DLEU1 is closely related to lymphatic metastasis, distant metastasis, and poor prognosis of ccRCC. It aggravates the progression of ccRCC by targeting miRNA-194-5p.

Long noncoding RNA DLEU1 aggravates osteosarcoma carcinogenesis via regulating the miR-671-5p/DDX5 axis

Long non-coding RNAs (LncRNAs) have been proven to be involved in the progression of osteosarcoma. LncRNA DLEU1 was found to act as an oncogene in various types of cancer. In this study, we aimed to explore the biological functions of DLEU1 in osteosarcoma and the specific mechanism. Our results showed that DLEU1 was highly expressed in osteosarcoma tissue specimens and cells. Downregulation of DLEU1 in osteosarcoma cells inhibited the cell proliferation, migration and invasion. Further mechanistic analysis and functional assays demonstrated that DLEU1 exerted its role by sponging microRNA (miR)-671-5p in osteosarcoma cells. Moreover, DEAD-box helicase 5 (DDX5) was confirmed as the target of miR-671-5p. Furthermore, rescue assays indicated that miR-671-5p inhibitor significantly reversed the effects of DLEU1 knockdown on osteosarcoma cell proliferation and invasion while restoration of DDX5 rescued the proliferation and invasion of osteosarcoma cells transfected with miR-671-5p mimics. In conclusion, DLEU1 acted as an oncogene in osteosarcoma by directly sponging miR-671-5p and regulating the expression of DDX5. These findings suggested that DLEU1 might be a novel therapeutic target in the treatment of osteosarcoma.

Long Non-coding RNA DLEU1 Promotes Cell Proliferation, Invasion, and Confers Cisplatin Resistance in Bladder Cancer by Regulating the miR-99b/HS3ST3B1 Axis.

Although accumulating evidence has shown the important function of long non-coding RNAs (lncRNAs) in tumor progression and chemotherapy resistance, the role of lncRNA DLEU1 in regulating proliferation, invasion, and chemoresistance of bladder cancer (BCA) cells remains largely unknown. Here, we found that DLEU1 was upregulated in BLCA tissues and BCA patients with high DLEU1 expression exhibited a shorter survival time. Furthermore, mechanistic analysis and functional assays validated that DLEU1 induced cell proliferation, invasion, and cisplatin resistance of BCA cells by de-repressing the expression of HS3ST3B1 through sponging miR-99b. Low miR-99b and high HS3ST3B1 levels were correlated with worse prognosis in patients with BCA. Ectopic expression of HS3ST3B1 or inhibition of miR-99b reversed DLEU1 knockdown-mediated suppression of cell proliferation, invasion, and cisplatin resistance. Thus, our study revealed a novel role for the DLEU1/miR-99b/HS3ST3B1 axis in regulating proliferation, invasion, and cisplatin resistance of BCA cells.

LncRNA DLEU1 contributes to colorectal cancer progression via activation of KPNA3

BackgroundAccumulating evidences show that long noncoding RNAs (lncRNA) play essential roles in the development and progression of various malignancies. However, their functions remains poorly understood and many lncRNAs have not been defined in colorectal cancer (CRC). In this study, we investigated the role of DLEU1 in CRC.MethodsQuantitative real-time PCR was used to detect the expression of DLEU1 and survival analysis was adopted to explore the association between DLEU1 expression and the prognosis of CRC patients. CRC cells were stably transfected with lentivirus approach and cell proliferation, migration, invasion and cell apoptosis, as well as tumorigenesis in nude mice were performed to assess the effects of DLEU1 in BCa. Biotin-coupled probe pull down assay, RNA immunoprecipitation and Fluorescence in situ hybridization assays were conducted to confirm the relationship between DLEU1 and SMARCA1.ResultsHere we revealed that DLEU1 was crucial for activation of KPNA3 by recruiting SMARCA1, an essential subunit of the NURF chromatin remodeling complex, in CRC. DLEU1 was indispensible for the deposition of SMARCA1 at the promoter of KPNA3 gene. Increased expression of DLEU1 and KPNA3 was observed in human CRC tissues. And higher expression of DLEU1 or KPNA3 in patients indicates lower survival rate and poorer prognosis. DLEU1 knockdown remarkably inhibited CRC cell proliferation, migration and invasion in vitro and in vivo while overexpressing KPNA3 in the meantime reversed it.ConclusionsOur results identify DLEU1 as a key regulator by a novel DLEU1/SMARCA1/KPNA3 axis in CRC development and progression, which may provide a potential biomarker and therapeutic target for the management of CRC.

LncRNA DLEU1 contributes to tumorigenesis and development of endometrial carcinoma by targeting mTOR.

lncRNA DLEU1 as a non-coding gene, involves in the occurrence and development of multiple tumors. However, there is no related report in endometrial carcinoma. In order to focus on the role and mechanism of lncRNA DLEU1 in endometrial carcinoma, we used qRT-PCR to detect the expression of lncRNA DLEU1 and found that lncRNA DLEU1 was highly expressed in endometrial carcinoma compared to normal endometrium. Moreover, compared to Ishikawa and KLE, lncRNA DLEU1 was higher in HEC-1B. In addition, up-regulation of lncRNA DLEU1 promoted cell viability, migration, invasion, and reduced the proportion of apoptosis. Otherwise, down-regulation of lncRNA DLEU1 produced opposite results. Xenograft nude mice model assay showed that lncRNA DLEU1 can promote tumorigenesis in vivo. RiP confirmed that lncRNA DLEU1 could bind to mTOR. The rescue experiments revealed that silence of mTOR after up-regulation of lncRNA DLEU1 resulted in decrease of cell viability, migration, and invasion and increase of apoptosis. The expression changes of PI3K, AKT1, p70S6K, rpS6, GSK3β, STAT3, and Bcl-xl were consistent with lncRNA DLEU1 and mTOR in Western blot. Thus, we suggest that lncRNA DLEU1 combines with mTOR and then increases the expression of PI3K/AKT/mTOR pathway to promote endometrial carcinoma tumorigenesis and progression. The present discovery has probability to provide a biomarker and lay the foundation for targeted therapy of endometrial carcinoma.

DLEU1 contributes to ovarian carcinoma tumourigenesis and development by interacting with miR-490-3p and altering CDK1 expression.

Recently, a large number of studies have focused on the important role of long non‐coding RNAs (lncRNAs) in metabolism and development and have found that abnormal lncRNA expression is associated with the pathogenesis and development of many diseases. The lncRNA DLEU1 is involved in many solid tumours and haematological malignancies. However, its role in epithelial ovarian carcinoma (EOC) and the associated molecular mechanisms has not been reported. In this study, quantitative reverse transcription–PCR (qRT–PCR) demonstrated higher lncRNA DLEU1 expression in EOC tissues than in normal tissues. Plasmid transfection of DLEU1 to up‐regulate its expression in the ovarian cancer cell lines A2780 and OVCAR3 increased cell proliferation, migration, and invasion, while inhibited apoptosis. Nude mouse xenograft assay demonstrated that DLEU1 overexpression promoted tumour growth in vivo. QRT–PCR showed decreased miR‐490‐3p expression, while Western blotting demonstrated increased its target genes CDK1, cyclinD1 and SMARCD1, as well as matrix metalloproteinase‐2 (MMP2), Bcl‐xL and P70S6K protein expression, respectively. Short interfering RNA silencing of DLEU1 produced opposite results, where qRT–PCR showed increased miR‐490‐3p expression. The dual‐luciferase reporter assay revealed a direct interaction between DLEU1 and miR‐490‐3p. MiR‐490‐3p plays a tumour suppressor role in epithelial ovarian cancer by targeting CDK1 regulation and influencing SMARCD1 and cyclin D1 (CCND1) expressions. Therefore, we suggest that through interaction with miR‐490‐3p, DLEU1 may influence the expression of CDK1, CCND1 and SMARCD1 protein, subsequently promoting the development and progression of EOC.