Colorectal Neoplasia Differentially Expressed Knockdown Research Articles

LncRNA CRNDE promotes hepatoma cell proliferation by regulating the metabolic reprogramming of M2 macrophages via ERK pathway

BackgroundLncRNA colorectal neoplasia differentially expressed (CRNDE) was found to be an important regulator in many cancers. This project focuses on the function of CRNDE on macrophage metabolic reprogramming and Hepatocellular carcinoma (HCC).MethodqRT-PCR and Immunofluorescence were used to analyze Arg-1, IL-10, CD163, CCL-18, CD206, and CRNDE expression in HCC tissues and macrophages. Western Blotting was used to analyze ERK and p-ERK expression. Edu assay, transwell assay and xenograft experiments were carried out to study cell viability, migrated and invasive capability. Immunohistochemical staining was used to evaluate Ki67 expression. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) was performed for macrophages metabolites analysis.ResultsArg-1, IL-10, CD163, CD206, and CRNDE were significantly up-regulated in HCC tissues, M2 macrophage and M0 macrophage with CRNDE overexpressed (OV-CRNDE-M0), which downregulated in M0 macrophage with CRNDE knockdown (sh-CRNDE-M0). The conditioned medium (CM) of M2 cells and OV-CRNDE-M0 cells promoted cell viability, invasion, and migration of HCC cells, the effect was reversed by sh-CRNDE-M0 cells CM. OV-CRNDE-M0 cells promoted tumor growth, Ki67 and CD206 expression in xenograft model. 61 metabolites were detected, of which 18 metabolites changed significantly in OV-CRNDE-M0 group compared to M0 group, with 9 upregulated and 9 downregulated. KEGG analysis showed the enrichment pathways were biosynthesis, glyoxylate and dicarboxylate metabolism. SMPDB analysis showed the enrichment pathways were hypoacetylaspartia, canavan disease, and aspartate metabolism.ConclusionCRNDE regulated the metabolic reprogramming of M2 macrophage via ERK pathway, which thereby contributed to HCC proliferation, migration, and invasion.

Long term exercise-derived exosomal LncRNA CRNDE mitigates myocardial infarction injury through miR-489-3p/Nrf2 signaling axis

Myocardial infarction (MI) is a cardiovascular disease and troubles patients all over the world. Exosomes produced after long-term exercise training were discovered to mediate intercellular communication and alleviate MI-induced heart injury. However, the detailed roles of long-term exercise-derived exosomal long noncoding RNAs (LncRNAs) in MI remain uncovered. In this study, we collected and identified long-term exercise-derived exosomes, and established MI or hypoxia/reoxygenation (H/R) model after LncRNA colorectal neoplasia differentially expressed (CRNDE) depletion. This work proved that LncRNA CRNDE was highly expressed in long-term exercise-derived exosomes (p = 0.0078). CRNDE knockdown increased cardiomyocytes apoptosis and oxidative stress (p = 0.0036), and suppressed MI progress (p = 0.0005). CRNDE served as the sponge of miR-489-3p to affect Nrf2 expression (p = 0.0001). MiR-489-3p inhibition effectively reversed the effects of CRNDE depletion on hypoxia cardiomyocytes (p = 0.0002). These findings offered a promising therapeutic option for the treatment of MI.

CRNDE, an enhancer RNA of prognostic value in glioma, correlates with immune infiltration: A pan-cancer analysis

Background: Recent evidence has emerged regarding the modification of the relationship between the enhancer RNA (eRNA) colorectal neoplasia differentially expressed (CRNDE) and the prognosis of patients with cancer. Nevertheless, the role of CRNDE in pan-cancer and tumour immune microenvironment (TIME) remains largely unexplored. Methods: Multiple bioinformatic methods were employed to unravel the role of elncRNA CRNDE in a wide range of cancers from the perspective of the expression patterns, prognosis, tumour immunity, and the association between CRNDE and its target gene IRX5 based on the public database. A nomogram was created by integrating independent factors. Gene set enrichment analysis (GSEA) was used to determine the potential signalling pathway mechanisms. Molecular biology experiments including RT-qPCR, MTT, Transwell, and wound-healing analyses were performed to evaluate the proliferation, migration, and invasion of glioma cells. Finally, RT-qPCR and immunohistochemistry were performed to analyse the expression and function of CRNDE in gliomas of different grades. Nissl staining was used to evaluate the potential effects of CRNDE knockdown in glioblastoma tissues. Results: CRNDE was dysregulated and associated with clinical features in 15 of the 33 cancer types. The survival analysis showed that high CRNDE expression might lead to a worsened prognosis among the six cancer types. CRNDE might be involved in immune regulation in multiple cancer types. CRNDE correlated with multiple tumours and immune-related pathways. Additionally, CRNDE knockdown inhibited glioma cell proliferation, migration, and invasion. Nissl staining confirmed that CRNDE siRNA notably decreased tumour growth. A stronger correlation between immune cells and CRNDE/IRX5 in lower-grade glioma than in glioblastoma multiforme tissues, and an association with IRX5 and immune checkpoint gene NRP1 were observed. Conclusions: An Enhancer RNA CRNDE may serve as a biomarker for cancer immunologic infiltration and poor prognosis, providing a new approach for cancer treatment.

Comprehensive Analysis of the Prognostic Value and Molecular Function of CRNDE in Glioma at Bulk and Single-Cell Levels.

Colorectal neoplasia differentially expressed (CRNDE) is an oncogenic long noncoding RNA (lncRNA) overexpressed in diverse malignancies. Here, we comprehensively analyze the prognostic value and molecular function of CRNDE in glioma. Bulk RNA-sequencing data from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA), and single-cell RNA-sequencing data from the Tumor Immune Single-Cell Hub (TISCH) were analyzed. Kaplan-Meier survival analysis was applied to verify the prognostic value of CRNDE. Then, a nomogram based on multivariate Cox regression was established for individualized survival prediction. Subsequently, the expression characteristic and biological function of CRNDE were analyzed at the single-cell level. Lastly, the effects of CRNDE on the proliferation and invasion of glioma cell were explored in vitro. We discovered that CRNDE was a powerful marker for risk stratification of glioma patients. Regardless of the status of IDH and 1p/19q, CRNDE could effectively stratify patients' prognosis. The nomogram that incorporated the CRNDE expression was proved to be a reliable tool for survival prediction. In addition, epithelial-mesenchymal transition may be the most important biological process regulated by CRNDE, which was identified at both the bulk and single-cell levels. Moreover, CRNDE knockdown significantly inhibited the proliferation and invasion of glioma cell. Overall, CRNDE is a vital oncogene and may be a valuable supplement to improve the clinical stratification of glioma.

LncRNA CRNDE Deteriorates Delayed Encephalopathy After Acute Carbon Monoxide Poisoning to Inactivate AKT/GSK3β/β-catenin Pathway via miR-212-5p.

Delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) is the most serious sequel of acute CO poisoning, with structure or function injury of the brain. LncRNA colorectal neoplasia differentially expressed (CRNDE) aberrant expression was involved in nerve cell injury; however, the mechanism of CRNDE in DEACMP remains elusive. CO poisoning model of Sprague-Dawley rats was established. Neurological function was measured by Morris water maze (MWM) testing. Histopathological condition of brain and hippocampus tissues was observed by hematoxylin and eosin (H&E), Nissl, and TUNEL staining. Pro-inflammatory cytokine levels were evaluated by enzyme-linked immunosorbent assay (ELISA). Oxidative damage and apoptosis markers were determined by related detection assays. Cell apoptosis were evaluated by flow cytometry analysis. Luciferase report and RNA immunoprecipitation (RIP) assays were employed to identify the binding relationship of CRNDE and miR-212-5p. CRNDE was significantly increased in CO poisoning animal model and oxygen-glucose deprivation (OGD) group, while that of miR-212-5p was decreased. CRNDE knockdown repressed the histopathological damage and apoptosis of brain and hippocampus tissues. Besides, CRNDE suppressed the AKT/GSK3β/β-catenin signaling pathway via targeting miR-212-5p. Furthermore, the protective effects of CRNDE silencing on brain tissue injury and apoptosis and AKT/GSK3β/β-catenin signaling pathway were reversed by inhibition of miR-212-5p in CO poisoning model. Collectively, CRNDE, serving as a sponge of miR-212-5p, aggravated the injury and apoptosis of brain and hippocampus tissues through regulating AKT/GSK3β/β-catenin signaling pathway under the CO-poisoning and OGD-treated model, suggesting a selected therapeutic target of DEACMP.

Exosomal transfer of activated neutrophil-derived lncRNA CRNDE promotes proliferation and migration of airway smooth muscle cells in asthma.

Activated neutrophil-derived exosomes reportedly contribute to the proliferation of airway smooth muscle cells (ASMCs), thereby aggravating the airway wall remodeling during asthma; however, the specific mechanism remains unclear. Lipopolysaccharide (LPS)-EXO and si-CRNDE-EXO were extracted from the media of human neutrophils treated with LPS and LPS + si-CRNDE (a siRNA targets long non-coding RNA CRNDE), respectively. Human ASMCs were co-cultured with LPS-EXO or si-CRNDE-EXO, and cell viability, proliferation and migration were measured. The interplay of colorectal neoplasia differentially expressed (CRNDE), inhibitor of nuclear factor kappa B kinase subunit beta (IKKβ) and nuclear receptor subfamily 2 group C member 2 (TAK1) was explored using RNA immunoprecipitation (RIP) and Co-IP assays. A mouse model of asthma was induced using ovalbumin. CRNDE was upregulated in LPS-EXO and successfully transferred from LPS-treated neutrophils to ASMCs through exosome. Mechanically, CRNDE loaded in LPS-EXO reinforced TAK1-mediated IKKβ phosphorylation, thereby activating the nuclear factor kappa B (NF-κB) pathway. Functionally, silencing CRNDE in LPS-EXO, an IKKβ inhibitor, and an NF-κB inhibitor all removed the upregulation of cell viability, proliferation and migration induced by LPS-EXO in ASMCs. In the end, the in vivo experiment demonstrated that CRNDE knockdown in neutrophils effectively reduced the thickness of bronchial smooth muscle in a mouse model for asthma. Activated neutrophils-derived CRNDE was transferred to ASMCs through exosomes and activated the NF-κB pathway by enhancing IKKβ phosphorylation. The latter promoted the proliferation and migration of ASMCs and then contributed to airway remodeling in asthma.

Oncogenic role of lncRNA CRNDE in acute promyelocytic leukemia and NPM1-mutant acute myeloid leukemia

The PML/RARα fusion protein acts in concert with cooperative genetic events in the development of acute promyelocytic leukemia (APL). However, oncogenic long non-coding RNAs (lncRNAs) cooperating with PML/RARα remain under-explored. Here, we first identified a set of pathogenesis-related lncRNAs, aberrantly expressed in APL using RNA-seq data from a large cohort of acute myeloid leukemia (AML) patients and normal counterparts. Among the pathogenesis-related lncRNAs, one of the evolutionarily conservative lncRNAs CRNDE (Colorectal Neoplasia Differentially Expressed) drew our attention. We found that CRNDE was highly expressed in the disease state but not in the preleukemic stage of APL, suggesting that CRNDE might be a secondary event coordinating with PML/RARα to promote APL development. Functional analysis showed that CRNDE knockdown induced differentiation and inhibited proliferation of APL cells, and prolonged survival of APL mice. Further mechanistic studies showed that CRNDE elicited its oncogenic effects through binding the miR-181 family and thereby regulating NOTCH2. Finally, we found that high CRNDE expression was also significantly correlated with NPM1 mutations and contributed to the differentiation block in NPM1-mutant AML. Collectively, our findings shed light on the importance of oncogenic lncRNAs in the development of AML and provide a promising target for AML therapy.

LncRNA CRNDE facilitates epigenetic suppression of CELF2 and LATS2 to promote proliferation, migration and chemoresistance in hepatocellular carcinoma

Our study aimed to investigate the expression, functional significance, and related mechanism of long noncoding RNA CRNDE (colorectal neoplasia differentially expressed) in hepatocellular carcinoma (HCC) pathogenesis. The resulted revealed that CRNDE was significantly overexpressed in HCC tissues and cell lines, and was statistically correlated with poor clinical outcome. CRNDE knockdown markedly decreased HCC cell proliferation, migration, and chemoresistance. In addition, in vivo experiments confirmed the suppressive effect of CRNDE knockdown on HCC progression. Mechanically, CRNDE directly bound to EZH2 (enhancer of zeste homolog), SUZ12 (suppressor of zeste 12), SUV39H1, and mediated their inhibition of tumor suppressor genes, including CUGBP Elav-like family member 2 (CELF2) and large tumor suppressor 2 (LATS2). CELF2 exerted tumor suppressive effect in HCC and was involved in CRNDE-mediated oncogenic effect. In addition, the oncogenic effects of CRNDE on HCC proliferation, migration and tumorigenesis, as well as its inhibition of Hippo pathway were abolished by LATS2 overexpression. Together, our work demonstrated the importance of CRNDE in HCC progression and elucidated the underlying molecular mechanisms. These findings provided new insights into HCC pathogenesis and chemoresistance mediated by CRNDE.

Knockdown of LncRNA CRNDE suppresses proliferation and P-glycoprotein-mediated multidrug resistance in acute myelocytic leukemia through the Wnt/β-catenin pathway.

Mechanisms involved in non-coding RNAs have been implicated in multidrug resistance (MDR) of acute myeloid leukemia (AML). Long non-coding RNA (lncRNAs) colorectal neoplasia differentially expressed (CRNDE) is reported to be involved in the malignant progression in AML. The purpose of the present study is to explore the roles and potential molecular mechanism of CRNDE in the MDR in AML. In our study, we confirmed that the expression of CRNDE was significantly up-regulated in patients with AML, especially in AML patients after adriamycin (ADR)-based chemotherapy. Spearman correlation analysis showed a positive correlation between the levels of CRNDE and MDR1 in AML patients after ADR-based chemotherapy. Moreover, CRNDE was up-regulated in AML cells, especially in ADR-resistant AML cells. Multidrug resistance protein 1 (MDR1)/p-glycoprotein (P-gp) levels were significantly increased in ADR-resistant AML cells, compared with parental AML cells. CRNDE down-regulation inhibited cell proliferation, promoted apoptosis, reduced Ki67 expression and enhanced cleaved caspase-3 expression in AML and ADR-resistant AML cells. In addition, CRNDE knockdown led to down-regulation of P-gp/MDR1, β-catenin, c-Myc and cyclinD1 expression, and enhanced the drug sensitivity to ADR in ADR-resistant AML cells. In conclusion, knockdown of CRNDE suppresses proliferation and P-gp-mediated MDR in ADR-resistant AML cells via inhibiting the Wnt/β-catenin pathway, suggesting that repression of CRNDE might be a therapeutic target to reverse MDR of ADR-resistant AML cells.

LncRNA CRNDE is activated by SP1 and promotes osteosarcoma proliferation, invasion, and epithelial-mesenchymal transition via Wnt/β-catenin signaling pathway.

Long noncoding RNAs (lncRNAs) were identified as a vital part in the development and progression of cancer in recent years. Colorectal neoplasia differentially expressed (CRNDE), a lncRNA, functions as an oncogene in some malignant neoplasias, but its role in the progression of osteosarcoma (OS) is still poorly understood. To dissect the difference in the expression of CRNDE, quantitative real-time polymerase chain reaction was utilized to evaluate it in OS tissues and cell lines (U2OS, MG63, and MNNG/HOS) compared with that in the adjacent normal tissues/osteoblast cells (hFOB1.19). The role of CRNDE in OS lines was assessed using Cell Counting Kit-8, colony formation, 5-ethynyl-2'-deoxyuridine staining, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling staining, flow cytometry, Transwell assays, and Western blot, respectively. The results demonstrated that the expression of CRNDE was high in OS tissues and cell lines, and partly induced by SP1. CRNDE knockdown attenuated OS cell proliferation and invasion and induced apoptosis and G0/G1 arrest. Moreover, the expression of mesenchymal markers N-cadherin, Vimentin and Snail were downregulated, while the expression of epithelial markers E-cadherin and ZO-1 were conversely upregulated due to CRNDE knockdown. The mechanistic investigations showed that CRNDE promoted glycogen synthase kinase-3β phosphorylation to activate the Wnt/β-catenin pathway. The results suggested that lncRNA CRNDE indeed contributed to OS proliferation, invasion, and epithelial-mesenchymal transition, working as an oncogene, demonstrating that lncRNA CRNDE may be a valid therapeutic target for the OS.

Down-regulation of LncRNA CRNDE aggravates kidney injury via increasing MiR-181a-5p in sepsis

Long non-coding RNA (lncRNA) colorectal neoplasia differentially expressed (CRNDE) is reported to be linked to inflammation and cell apoptosis. However its role in sepsis induced kidney injury remains unclear. This study aims to explore the possible mechanism of CRNDE in kidney injury induced by sepsis. In vivo urine-derived sepsis (US) rat model and in vitro LPS-induced HK-2 and HEK293 cells were established. Kidney function was measured in rats from different groups. Relative levels of tumor necrosis factor-α (TNF-α) and interleukin-1β(IL-1β) in kidney tissue were detected via Enzyme-linked immune sorbent assay (ELISA). Then we up- or down-regulated CRNDE and miRNA-181a-5p expression in the cells. The biological influence of CRNDE and miR-181a-5p on cells was studied using CCK-8 assay and Annexin V assay. Interaction between CRNDE and miR-181a-5p was determined by bioinformatics analysis, RT-PCR, and dual luciferase reporter assay. Peroxisome proliferator-activated receptor-α (PPARα) and cell apoptosis related molecules were detected by western blot. We demonstrated that CRNDE was markedly down-regulated while miR-181a-5p was significantly up-regulated in sepsis models. CRNDE interacted with miR-181a-5p, and negatively regulated its expression level. CRNDE knockdown in rats increased the urea nitrogen and serum creatinine in plasma. Knockdown of CRNDE or transfection of miR-181a-5p significantly inhibited proliferation and promoted apoptosis of HK-2 and HEK293 cells, while overexpression of CRNDE and transfection of miR-181a-5p inhibitors had opposite effects. For mechanism, miR-181a-5p directly targeted the 3′ untranslated region of PPARα, and depressed its protein level, and PPARα was regulated indirectly by CRNDE. We concluded that CRNDE protected renal cell from sepsis-induced injury via miR-181a-5p/PPARα pathway.

Transcriptome analysis-identified long noncoding RNA CRNDE in maintaining endothelial cell proliferation, migration, and tube formation

Obesity is a leading risk factor for type-2 diabetes. Diabetes often leads to the dysregulation of angiogenesis, although the mechanism is not fully understood. Previously, long noncoding RNAs (lncRNAs) have been found to modulate angiogenesis. In this study, we asked how the expression levels of lncRNAs change in endothelial cells in response to excessive palmitic acid treatment, an obesity-like condition. Bioinformatics analysis revealed that 305 protein-coding transcripts were upregulated and 70 were downregulated, while 64 lncRNAs were upregulated and 46 were downregulated. Gene ontology and pathway analysis identified endoplasmic reticulum stress, HIF-1 signaling, and Toll-like receptor signaling as enriched after palmitic acid treatment. Moreover, we newly report enrichment of AGE-RAGE signaling pathway in diabetic complications, IL-17 signaling, and cysteine and methionine metabolism by palmitic acid. One lncRNA, Colorectal Neoplasia Differentially Expressed (CRNDE), was selected for further investigation. Palmitic acid induces CRNDE expression by 1.9-fold. We observed that CRNDE knockdown decreases endothelial cell proliferation, migration, and capillary tube formation. These decreases are synergistic under palmitic acid stress. These data demonstrated that lncRNA CRNDE is a regulator of endothelial cell proliferation, migration, and tube formation in response to palmitic acid, and a potential target for therapies treating the complications of obesity-induced diabetes.

Long non-coding RNA CRNDE enhances cervical cancer progression by suppressing PUMA expression

Cervical cancer is the second most common gynecological malignancy, and it remains a leading cause of tumor-related death among female in the world. Long non-coding RNAs (lncRNAs) have been indicated to play essential roles in tumorigenesis, and the lncRNA colorectal neoplasia differentially expressed (CRNDE) is increased in several tumors. Nevertheless, little is known about the effects of lncRNA CRNDE on human cervical cancer. The aim of the study was to explore the clinical significance of lncRNA CRNDE expression in human cervical cancer. Our results indicated that CRNDE expression was increased in cervical cancer tissues and several cervical cancer cell lines. Through loss-of-function and gain-of-function approaches, we found that CRNDE knockdown markedly reduced cervical cancer cell proliferation, while CRNDE overexpression significantly promoted cervical cancer cell growth. Consistently, CRNDE decreasing obviously inhibited tumorigenicity of cervical cancer cells in vivo, whereas CRNDE increasing markedly promoted cervical cancer progression. Mechanistically, we verified that CRNDE bond to p53 upregulated modulator of apoptosis (PUMA), and PUMA was required for CRNDE to enhance cervical cancer cell growth. Our study demonstrated that CRNDE, combined with PUMA, could be utilized as factor for the clinical diagnosis and prognosis of cervical cancer, and might be potential target for developing effective therapeutic strategy to prevent cervical cancer progression.

LncRNA Colorectal Neoplasia Differentially Expressed (CRNDE) Promotes Proliferation and Inhibits Apoptosis in Non-Small Cell Lung Cancer Cells by Regulating the miR-641/CDK6 Axis.

BackgroundThe lncRNA Colorectal Neoplasia Differentially Expressed (CRNDE) gene has been reported as a potential oncogene in NSCLC. Nevertheless, the molecular mechanism of CRNDE in NSCLC progression remains largely unknown.Material/MethodsqRT-PCR assay was performed to detect the expression levels of CRNDE, miR-641, and cyclin-dependent kinase 6 (CDK6) in NSCLC. Western blot assay was employed to assess CDK6 protein level in treated NSCLC cells. si-CRNDE#1, si-CRNDE#2, miR-641 mimics, miR-641 inhibitors, or Vector-CDK6 were transfected into NSCLC cells to change the expression levels of CRNDE, miR-641, or CDK6. Dual-luciferase reporter assay was performed to validate the direct interrelated miRNA of CRNDE and the potential target of miR-641. MTT and flow cytometry assays were performed to assess the capacities of cell proliferation and apoptosis, respectively.ResultsCRNDE level was upregulated in NSCLC, and its knockdown suppressed NSCLC cells proliferation and enhanced apoptosis, whereas miR-641 antagonized the regulatory effect of CRNDE knockdown by directly binding to CRNDE. Moreover, CDK6 was a target of miR-641 and miR-641 exerted anti-proliferation and pro-apoptosis effects through CDK6.ConclusionsCRNDE promoted proliferation and inhibited apoptosis of NSCLC cells at least in part by regulating the miR-641/CDK6 axis, suggesting that CRNDE is a potential therapeutic target for NSCLC treatment.

LncRNA CRNDE promotes the epithelial-mesenchymal transition of hepatocellular carcinoma cells via enhancing the Wnt/β-catenin signaling pathway.

Colorectal neoplasia differentially expressed (CRNDE) is a significantly upregulated long noncoding RNA in hepatocellular carcinoma (HCC). CRNDE could promote cell proliferation, migration, and invasion, while its molecular mechanisms were still largely unclear. In this study, we investigated the expression and function of CRNDE. CRNDE was significantly upregulated in tumor tissues compared with adjacent normal tissues. In vitro, we revealed that knockdown of CRNDE inhibited cell proliferation, migration, and cell invasion capacities in HCC. Animal studies indicated that CRNDE knockdown represses both growth and metastasis of HCC tumors in vivo. Moreover, knockdown of CRNDE suppressed the cell epithelial‐mesenchymal transition (EMT) process by increasing the expression of E‐cadherin and ZO‐1, whereas, decreasing the expression of N‐cadherin, slug, twist, and vimentin in HCC cells. We also revealed that knockdown of CRNDE suppressed the Wnt/β‐catenin signaling in HCC. Thus, CRNDE could modulate EMT of HCC cells and knockdown of CRNDE impaired the mesenchymal properties. CRNDE increased invasion of HCC cells might be through activating the Wnt/β‐catenin signaling pathway.

Long non-coding RNA CRNDE may be associated with poor prognosis by promoting proliferation and inhibiting apoptosis of cervical cancer cells through targeting PI3K/AKT.

Long non-coding RNAs (lncRNAs) are attracting more and more attention from researchers because they are relatively new factors in regulating biological processes in human cancers. The Colorectal Neoplasia Differentially Expressed (CRNDE) lncRNA is transcribed from chromosome 16 on the opposite strand to the neighboring IRX5 gene. It was originally discovered abnormally expressed in colorectal cancer (CRC) and was certified a critical biomarker in many cancers. However, its biological function and mechanism underlying the tumorigenesis of cervical cancer still require exploration. This study confirmed that CRNDE is markedly up-regulated in clinical tissues and cell lines of cervical cancer. The high expression of CRNDE positively correlates with advanced FIGO stage and lymph node metastasis. Furthermore, the overall survival rate in the group with highly expressed CRNDE was worse, and the high level of CRNDE may be regarded a prognostic factor because of its results from proportional hazard analysis. Loss-of-function assays revealed that CRNDE influences proliferation and apoptosis in cervical cancer cells, and Western blot assays revealed that the PI3K/AKT pathway was inactivated in response to CRNDE knockdown. Therefore, we conclude that CRNDE exerts oncogenic function in cervical cancer and should be further explored as a novel prognostic predictor.

Long non-coding RNA CRNDE sponges miR-384 to promote proliferation and metastasis of pancreatic cancer cells through upregulating IRS1.

Colorectal neoplasia differentially expressed (CRNDE), a vital cancer-related long non-coding RNA (lncRNA), has been brought to reports for playing quintessential functions in the growth and progression of several human malignancies. Nevertheless, the expression as well as the functional mechanisms of CRNDE in pancreatic cancer is not known so for. This study aimed at investigating the biological and clinical importance of CRNDE in human pancreatic cancer. The expression levels of CRNDE in pancreatic cancer tissues as well as cell lines were identified with the help of quantitative real-time PCR (qRT-PCR). Furthermore, the analysis of the relationship between CRNDE expression and clinicopathologic characteristics of patients with pancreatic cancer was also performed. Novel target of CRNDE was identified with the use of bioinformatics analysis and confirmed by a dual-luciferase reporter assay. Colorectal neoplasia differentially expressed was knocked down using siRNA in pancreatic cancer cells. Thereafter, cell proliferation, migration and invasion were examined. Tumour xenograft was created to explore the function of CRNDE in tumorigenesis in vivo. Upregulation of the expression of CRNDE was found in pancreatic cancer tissues as well as cell lines, in comparison with the adjacent non-tumour tissues and human pancreatic duct epithelial cells. High expression of CRNDE was correlated with poor clinicpathological characteristics and shorter overall survival. We identified miR-384 as a direct target for CRNDE. Moreover, the CRNDE knockdown considerably inhibited pancreatic cancer cell proliferation, migration and invasion not only in vitro but also in vivo. In addition, CRNDE positively regulated IRS1 expression through sponging miR-384. Colorectal neoplasia differentially expressed performed an oncogenic function in cell proliferation as well as metastasis of pancreatic cancer. Our results suggest that CRNDE is likely to serve as an efficient therapeutic approach in respect of pancreatic cancer treatment.

Long Noncoding RNA CRNDE Promotes Multiple Myeloma Cell Growth by Suppressing miR-451.

It has been determined that long noncoding RNAs (lncRNAs) are identified as a potential regulatory factor in multiple tumors as well as multiple myeloma (MM). However, the role of colorectal neoplasia differentially expressed (CRNDE) in the pathogenesis of MM remains unclear. In this study, we found that the CRNDE expression level, in MM samples and cell lines, is higher than that in the control detected by real-time qPCR, which is also closely related to tumor progression and poor survival in MM patients. Knockdown of CRNDE significantly inhibits the proliferative vitality of MM cells (U266 and RPMI-8226), induces cell cycle arrest in the G0/G1 phase, and promotes apoptosis. After being transfected with siRNA, miR-451 expression observably increases. Bioinformatics analysis and luciferase assay reveal the interaction by complementary bonding between CRNDE and miR-451. Pearson’s correlation shows that CRNDE is negatively correlated to miR-451 expression in human MM samples. Subsequently, miR-451 inhibitor rescues the inhibited tumorigenesis induced by CRNDE knockdown. Our study illustrates that lncRNA CRNDE induces the proliferation and antiapoptosis capability of MM by acting as a ceRNA or molecular sponge via negatively targeting miR-451, which could act as a novel diagnostic marker and therapeutic target for MM.

LncRNA CRNDE triggers inflammation through the TLR3-NF-κB-Cytokine signaling pathway.

Colorectal neoplasia differentially expressed (CRNDE), an oncogene, is highly expressed in many tumor cells and affects cellular proliferation, migration, invasion, and apoptosis. Its function and mechanism of action is a research hotspot. In this study, microarray analysis was performed to discover the differentially expressed genes in CRNDE over-expression cells. RT² Profiler PCR Array was used to study the expression of genes related to the toll-like receptor (TLR) pathway. We found that over-expression of CRNDE in astrocytes increased the expression of key factors in the toll-like receptor signaling pathway, especially toll-like receptor-3-mediated MyD88-independent pathway. Furthermore, it up-regulated expression levels of downstream transcription factor such as nuclear factor kappa B and numerous cytokines. In contrast, CRNDE knockdown in glioma U87MG cell line showed an opposite trend in the expression of the above-mentioned genes. We speculated that CRNDE might trigger inflammation to regulate tumorigenesis and tumor development through the toll-like receptor pathway.

GENT-24. LONG NON-CODING RNA CRNDE AS A POTENTIAL EGFR-REGULATED ONCOGENE IN GLIOMA

Long non-coding RNAs (lncRNAs) have recently been shown to play important roles in glioma development and progression. However, information on their functions and molecular mechanisms remains limited. Colorectal Neoplasia Differentially Expressed (CRNDE) is a novel lncRNA that has been found to be significantly upregulated in gliomas relative to normal brain tissues, and positively correlated with tumor grading. In the present study, we investigated the prognostic value of CRNDE and its underlying molecular mechanism in glioma. Based on two independent publicly accessible cohorts of glioblastoma multiforme patients treated with an uniform regimen, high CRNDE level was found to be associated with significantly poorer overall survival. Functional assays using three glioblastoma cell lines revealed that CRNDE knock-down could significantly inhibit glioma cell growth, increase cell apoptosis, induce cell cycle arrest at G0/G1 phase, and impair cell invasion. Further in vivo studies using a subcutaneous xenograft rodent model showed that cells with downregulated CRNDE expression exhibited significantly slower growth rate. We also identified a significant association between CRNDE expression and EGFR signaling in vitro. CRNDE expression was more abundant in EGFR-mutant samples than in EGFR-wild cases. Activation of EGFR signaling by EGF or inhibition by an EGFR-tyrosine kinase inhibitor in cell lines would enhance or suppress CRNDE expression, respectively. These findings suggest that CRNDE may potentially be under positive regulation by EGFR signaling, and may play a significant oncogenic role in glioma pathogenesis. CRNDE should be further explored as a potential biomarker and therapeutic target in glioma.