Non-coding RNA Colorectal Neoplasia Differentially Expressed Research Articles

Long Noncoding RNA CRNDE Promotes Gastric Cancer Progression through Targeting miR-136-5p/MIEN1.

Background: Long noncoding RNAs (lncRNAs) contribute to the initiation and progression of gastric cancer (GC). The purpose of this study is to examine the potential role of lncRNA colorectal neoplasia differentially expressed (CRNDE)in modulating the expression of migration and invasion enhancer 1 (MIEN1) through the suppression of miR-136-5p in GC. Methods: The biological roles of CRNDE, miR-136-5p, and MIEN1 in GC were assessed both in laboratory settings and through the examination of clinical samples. Results: CRNDEwas found to be significantly increased in GC tissues, and this upregulation was associated with an unfavorable prognosis of GC patients. In vitro experiments showed that inhibiting cell growth and migration, along with promoting apoptosis in GC cells, could be achieved by either disabling CRNDEor MIEN1, or by increasing the expression of miR-136-5p. MIEN1 is a specific recipient of miR-136-5p, and the anticancer effects of miR-136-5p can be counteracted by the increased expression of MIEN1. Through the examination of clinical specimens, it has been observed that there is a significant positive correlation between the expression of MIEN1 and CRNDE. In contrast, miR-136-5p expression in GC tissues shows a negative correlation. Conclusion: A previously unexplored therapeutic target for GC involves the CRNDE/miR-136-5p/MIEN1 signal transduction cascade.

Predictive value of prenatal ultrasound combined with long non-coding RNA CRNDE of women for their postpartum lower extremity deep venous thrombosis

Objective Deep vein thrombosis (DVT) is a common complication in obstetrics that needs early interaction. The study examined the expression change and clinical value of long non-coding RNA (lncRNA) colorectal neoplasia differentially expressed (CRNDE) in DVT early diagnosis. Methods One hundred patients with DVT after delivery and 100 healthy parturients without DVT were enrolled. Serum samples were collected one day before delivery and received qRT-PCR for mRNA detection. Prenatal coagulation markers including prothrombin time (PT), activated partial prothrombin time (APTT), fibrinogen (FIB) and thrombin time (TT), D-dimer (D-D), thrombomodulin (TM), and peroxidase anti-peroxidase soluble complex (PAP) were tested. The receiver operating characteristic (ROC) curve was drawn for the diagnostic value assessment. Results LncRNA CRNDE levels increased remarkably in the serum of DVT patients compared with the healthy controls, which were negatively correlated with serum concentration of PT, APTT, and TT while positively correlated with FIB, D-D, TM, and PAP. Serum CRNDE (HR = 5.973, 95% CI = 2.990–11.933, p < .001) was independently related to the occurrence of DVT after delivery. Then, ROC curve using serum CRNDE showed a good diagnostic value for DVT with the AUC of 0.899. ROC curve of ultrasonography combined with CRNDE produced an AUC of 0.968, and both sensitivity and specificity were enhanced compared to a single indicator. Conclusions The increase of CRNDE level was an independent risk factor for postpartum DVT. Prenatal ultrasonography combined with CRNDE can improve the predictive efficacy for DVT.

The long non-coding RNA CRNDE promotes osteosarcoma proliferation and migration by sponging miR-136-5p/MRP9 axis.

BackgroundThe long-noncoding RNA colorectal neoplasia differentially expressed (CRNDE) gene has been found to be upregulated in several solid tumors. Whether CRNDE affects osteosarcoma (OS) and its underling mechanism remains unknown.MethodsTumor tissues and corresponding normal tissues were collected from 45 patients with OS. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was applied to determine lncRNA CRNDE level in the tissues. Participants were divided into a high CRNDE group and a low CRNDE group according to the median value of lncRNA CRNDE expression detected by in situ hybridization (ISH). The differences between high and low expression of lncRNA CRNDE in patients were compared clinically by chi-square test. Kaplan-Meier survival analysis was applied to analyze the relationship between lncRNA CRNDE expression and patient survival. Subsequently, silencing or overexpression of lncRNA CRNDE were performed in MG63 and 143B cell lines, qRT-PCR was applied to verify the expression of lncRNA CRNDE, miR-136-5p, and MRP9; dual-luciferase reporter assay was used to evaluate the targeting relationship between miR-136-5p, lncRNA CRNDE, and Cell Counting Kit-8 (CCK8), wound-healing, and Transwell assays were used to analyze for cell proliferation, migration, and invasion, respectively, and western blot was used to detect expression in cells.ResultsThe expression of CRNDE in OS tissues was higher than that in normal tissues. High lncRNA CRNDE expression was significantly associated with clinical stage, lung metastasis, and poor prognosis in OS patients. Additionally, overexpression of lncRNA CRNDE promoted proliferation and migration of OS cells. Bioinformatics analysis showed that lncRNA CRNDE competitively inhibited miR-136-5p through acting as a competitive endogenous RNA (ceRNA). It was also revealed that miR-136-5p is a binding target gene of lncRNA CRNDE and that MRP9 is involved in this process as a downstream target gene of miR-136-5p.ConclusionsThe lncRNA CRNDE promotes the proliferation and migration of OS cells by regulating the miR-136-5p/MRP9 pathway, and lncRNA CRNDE can be a significant marker of OS prognosis.

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.

Long Non-Coding RNA CRNDE Is Involved in Resistance to EGFR Tyrosine Kinase Inhibitor in EGFR-Mutant Lung Cancer via eIF4A3/MUC1/EGFR Signaling.

(1) Background: Acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is an intractable problem for many clinical oncologists. The mechanisms of resistance to EGFR-TKIs are complex. Long non-coding RNAs (lncRNAs) may play an important role in cancer development and metastasis. However, the biological process between lncRNAs and drug resistance to EGFR-mutated lung cancer remains largely unknown. (2) Methods: Osimertinib- and afatinib-resistant EGFR-mutated lung cancer cells were established using a stepwise method. A microarray analysis of non-coding and coding RNAs was performed using parental and resistant EGFR-mutant non-small cell lung cancer (NSCLC) cells and evaluated by bioinformatics analysis through medical-industrial collaboration. (3) Results: Colorectal neoplasia differentially expressed (CRNDE) and DiGeorge syndrome critical region gene 5 (DGCR5) lncRNAs were highly expressed in EGFR-TKI-resistant cells by microarray analysis. RNA-protein binding analysis revealed eukaryotic translation initiation factor 4A3 (eIF4A3) bound in an overlapping manner to CRNDE and DGCR5. The CRNDE downregulates the expression of eIF4A3, mucin 1 (MUC1), and phospho-EGFR. Inhibition of CRNDE activated the eIF4A3/MUC1/EGFR signaling pathway and apoptotic activity, and restored sensitivity to EGFR-TKIs. (4) Conclusions: The results showed that CRNDE is associated with the development of resistance to EGFR-TKIs. CRNDE may be a novel therapeutic target to conquer EGFR-mutant NSCLC.

Long noncoding RNA CRNDE functions as a diagnostic and prognostic biomarker in osteosarcoma, as well aspromotes itsprogression via inhibition of miR-335-3p.

This study was performed to evaluate the diagnostic and prognostic value, as well as the role of long-chain noncoding RNA (lncRNA) colorectal neoplasia differentially expressed (CRNDE) in osteosarcoma (OS). A quantitative real-time polymerase chain reaction assay was to determine lncRNA CRNDE and microRNA-335-3p(miR-335-3p) expressions. The Kaplan-Meier analysis was to analyze the relationship between lncRNA CRNDE expression and survival in patients with OS. Receiver operating characteristic curves were to evaluate the diagnostic value of lncRNA CRNDE in OS. Bioinformatics analysis and luciferase reporter assays were used to predict and confirm the relationship between lncRNA CRNDE and miR-335-3p. Cell counting Kit-8 and transwell migration assays assessed the role of lncRNA CRNDE and miR-335-3p in OS cells. lncRNA CRNDE expression was upregulated and miR-355-3p expression was downregulated in OS. In patients with OS, low lncRNA CRNDE expression demonstrated higher overall survival, whereas high lncRNA CRNDE expression was an independent poor prognostic factor. Furthermore, increased lncRNA CRNDE expression was associated with distant metastasis and the tumor-node-metastasisstage in patients with OS, which can be considered as an independent diagnostic biomarker in OS. We revealed that miR-335-3p was the target of lncRNA CRNDE. It also demonstrated that knockdown of lncRNA CRNDE inhibited OS cell proliferation, migration, and invasion,and inhibition of miR-355-3p promoted this effect. Finally, miR-335-3p partially mediated the stimulatory effects of lncRNA CRNDE in OS. We demonstrated that lncRNA CRNDE is a potential diagnostic and prognostic biomarker for OS, and the lncRNA CRNDE/miR-335-3p axis participates in OS progression.

The long non-coding RNA CRNDE regulates growth of multiple myeloma cells via an effect on IL6 signalling

Multiple myeloma (MM) is a currently incurable malignancy of antibody-secreting plasma cells. Long non-coding RNAs (lncRNAs) have been recognised as an important class of regulatory molecules which are increasingly implicated in tumorigenesis. While recent studies have demonstrated changes in expression of lncRNAs in MM, the functional significance and molecular pathways downstream of these changes remain poorly characterised. In this study, we have performed CRISPR-mediated deletion of the locus encoding the lncRNA Colorectal Neoplasia Differentially Expressed (CRNDE), a known oncogenic lncRNA that is overexpressed in plasma cells of MM patients and is a marker of poor prognosis. We found that CRISPR-mediated deletion of the CRNDE locus in MM cells decreases proliferation and adhesion properties, increases sensitivity to Dexamethasone and reduces tumour growth in an in vivo xenograft model. Transcriptomic profiling in CRNDE-deleted MM cells demonstrated that CRNDE activates expression of a number of genes previously implicated in the aetiology of MM, including IL6R. We further demonstrate that deletion of the CRNDE locus diminishes IL6 signalling and proliferative responses in MM cells. Altogether this study reveals the IL6 signalling pathway as a novel mechanism by which CRNDE impacts upon MM cell growth and disease progression.

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.

Long non-coding RNA CRNDE promotes malignant progression of hepatocellular carcinoma through the miR-33a-5p/CDK6 axis.

Emerging evidence has suggested that long non-coding RNA (lncRNA) colorectal neoplasia differentially expressed (CRNDE) is upregulated in hepatocellular carcinoma (HCC) and is associated with cell invasion, migration, and growth. However, the potential modulation mechanism remains to be elucidated. MiR-33a-5p and cyclin-dependent kinase 6 (CDK6) also participate in the pathophysiology of HCC. This work aims to investigate the effect of CRNDE on HCC apoptosis, invasion, and migration and elucidate the role of miR-33a-5p and CDK6 therein. CRNDE and CDK6 were upregulated in HCC tissues and cells, while miR-33a-5p was downregulated. Inhibition of CRNDE suppressed the invasion, migration, and proliferation of HCC cells and enhanced apoptosis by modulating proteins associated with mitochondrial apoptosis (caspase 3, Bax, cytochrome-c, Bcl-2), which were the same as the function of miR-33a-5p overexpression. The dual-luciferase reporter assay demonstrated that miR-33a-5p was a target of CRNDE, and in turn, CRNDE inhibition enhanced the level of miR-33a-5p. CDK6 was also revealed as a target of miR-33a-5p, and both CRNDE inhibition and miR-33a-5p overexpression suppressed CDK6 expression and led to G0/G1 phase block in HCC cells. In vivo experiments using a mouse xenograft tumor model further verified the interaction between CRNDE and miR-33a-5p, showing that miR-33a-5p overexpression or CRNDE inhibition suppressed CDK6 expression and HCC tumorigenesis. Overall, the present work indicated that CRNDE plays an oncogenic function in HCC through regulating the miR-33a-5p/CDK6 axis, revealing a potential therapeutic target in HCC.

RETRACTED: Protective role of long noncoding RNA CRNDE in myocardial tissues from injury caused by sepsis through the microRNA-29a/SIRT1 axis

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of Editor-in-Chief and the corresponding author. The corresponding author confessed that the paper was outsourced to a third-party company, who could not guarantee the integrity of the data.

Long noncoding RNA CRNDE promotes proliferation, migration and invasion in prostate cancer through miR-101/Rap1A.

Prostate cancer (Pca) is the second frequent malignancy in men. Long noncoding RNAs (lncRNAs) have been reported to play essential roles in the progression of cancers, including Pca. LncRNA colorectal neoplasia differentially expressed (CRNDE) has been found to affect tumorigenesis in many cancers. However, the exact role and mechanism of CRNDE in Pca remain poorly understood. 64 Pca patients were recruited in this study. PC3 and 22RV1 cells were used in vitro experiments. The expressions of CRNDE, microRNA-101 (miR-101), and Ras-related protein 1A (Rap1A) were detected in vivo and in vitro by quantitative real-time polymerase chain reaction and western blot, respectively. Cell proliferation, apoptosis, migration, and invasion were investigated through cell counting kit-8, flow cytometry, and Transwell assays, respectively. The interaction between miR-101 and CRNDE or Rap1A was explored by bioinformatics analysis and luciferase reporter assay. High expression of CRNDE was shown in Pca tissues and cells and predicted poor outcomes of patients. Overexpression of CRNDE promoted cell proliferation, migration, and invasion but decreased apoptosis in Pca cells, while its knockdown showed an opposite effect. CRNDE was a decoy of miR-101 and its effect on Pca progression was reversed by miR-101. Rap1A was identified as a target of miR-101 and it attenuated the effect of miR-101 on Pca development. Moreover, the Rap1A protein level was positively regulated by CRNDE, which was weakened by miR-101. CRNDE contributed to cell proliferation, migration, and invasion by regulating the miR-101/Rap1A axis in Pca, providing a novel strategy for Pca treatment.

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.

Long non-coding RNA CRNDE regulates cell proliferation, migration, invasion, epithelial-mesenchymal transition and apoptosis in oral squamous cell carcinoma.

The present study aimed to investigate whether the long non-coding RNA (lncRNA) colorectal neoplasia differentially expressed (CRNDE) can promote the migration and invasion of human oral squamous cell carcinoma (OSCC) cells via the regulation of epithelial-mesenchymal transition (EMT). CAL-27 and SCC-15 cells were classified into a control group, a small interfering negative control (si-NC) group (cells transfected with control siRNA) and an si-CRNDE group (cells transfected with CRNDE siRNA). The expression of CRNDE in OSCC tissues and cell lines was detected by in situ hybridization (ISH) and reverse transcription-quantitative polymerase chain reaction. An MTT assay was used to detect cell proliferation, flow cytometry was performed to determine cell apoptosis, wound-healing and Transwell assays were conducted to evaluate cell metastasis, and immunofluorescence staining and western blotting were performed to measure the expression of proteins associated with EMT. Tumor-bearing mouse models were established, and the tumor volumes were recorded. An immunohistochemical assay was performed to determine the expression of EMT-related proteins. CRNDE expression was increased in OSCC tissues and cell lines compared with that in normal tissues and cell lines. Compared with the control group, the si-CRNDE group displayed a reduction in the expression of CRNDE, in the proliferation, migration and invasion of cells, in the protein expression of N-cadherin, vimentin and Snail, and in the expression of proteins in the Wnt/β-catenin pathway. However, an increase was displayed in the apoptosis of cells and the expression of E-cadherin. Compared with the control group of tumor-bearing nude mice, the sh-CRNDE group demonstrated slowed tumor growth, reduced tumor weight and elevated E-cadherin, as well as reduced expression of N-cadherin, vimentin and Snail. In conclusion, silencing CRNDE may inhibit EMT, thus decreasing the migration and invasion of human OSCC cells by repressing the activation of the Wnt/β-catenin signaling pathway, thereby restricting cell growth and promoting cell apoptosis.

Prognostic Value of Long Noncoding RNA CRNDE as a Novel Biomarker in Solid Cancers: An Updated Systematic Review and Meta-Analysis.

Background: Long noncoding RNA colorectal neoplasia differentially expressed (CRNDE) has been reported to exhibit a potential oncogenic role in the development of human cancers. However, the clinical value of CRNDE expression in various cancers still remains unclear. Herein, we conducted a meta-analysis to investigate the association between CRNDE and clinical outcomes in solid cancers.Methods: A systematic search was performed though the PubMed, EMBASE, Web of Science, Ovid, Cochrane library, CNKI and WanFang databases for eligible studies on clinical values of CRNDE in solid cancers. The pooled hazard ratios (HRs) or odd ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the link between CRNDE and clinical outcomes.Results: A total of 3690 patients from 20 studies (including 2 studies have 2 cohorts, respectively) were included. The results suggested that elevated CRNDE expression predicted a poor overall survival (OS) for in 13 types of solid cancers (HR=1.46, 95% CI: 1.33-1.58, P<0.001) with no heterogeneity (I2=21.8%, P=0.19). Subgroup analysis indicated a significant association between high CRNDE expression and shorter OS in the studies with digestive system cancers (HR=1.42, 95% CI: 1.28-1.55, P<0.001), qRT-PCR method (HR=1.45, 95% CI: 1.30-1.59, P<0.001), sample size >100 (HR=1.44, 95% CI: 1.32-1.57, P<0.001), and NOS>7 (HR= 1.50, 95% CI: 1.23-1.78, P<0.001). Furthermore, the pooled results showed that CRNDE was an independent prognostic factor for OS in cancer patients (HR=1.37, 95% CI: 1.22-1.52, P<0.001). In addition, we also revealed that CRNDE was positively related to tumor size (OR=2.10, 95%CI: 1.68-2.63, P<0.001), TNM stage (OR=2.86, 95%CI: 2.29-3.56, P<0.001), lymph node metastasis (LNM) (OR=3.21, 95%CI: 2.01-5.13, P<0.001), and distant metastasis (OR=4.36, 95%CI: 2.36-8.07, P<0.001). Although the probable evidences of publication bias were found in the studies with OS, tumor size, TNM stage or LNM, the trim and fill analysis confirmed the reliability of these results was not affected.Conclusion: Elevated CRNDE expression was associated with larger tumor size, advanced TNM stage, worse LNM and distant metastasis, and shorter OS, suggesting that CRNDE may act as an independent prognostic biomarker in solid cancers.

Long non-coding RNA CRNDE promote the progression of tongue squamous cell carcinoma through regulating the PI3K/AKT/mTOR signaling pathway.

Long non-coding RNAs (lnRNAs) colorectal neoplasia differentially expressed (CRNDE) has been identified as a crucial regulator involved in tongue squamous cell carcinoma (TSCC). However, the molecular mechanism of CRNDE involved in TSCC progression is still unknown. In the study, qRT-PCR assay was used to detect the expression of CRNDE in TSCC tissues and cells. CCK-8 assay, colony formation assay, transwell assay and flow cytometric analysis were performed to determine cell proliferation ability, colony formation, migration and invasion capacities, and cell apoptosis, respectively. Western blot was employed to assess the activity of the PI3K/AKT/mTOR pathway. A xenograft mice model was performed to evaluate the role of CRNDE on tumor growth in vivo. The results showed CRNDE was upregulated in TSCC tissues and cell lines. CRNDE knockdown repressed the proliferation, colony formation, migration and invasion and promoted apoptosis in TSCC cells. Moreover, CRNDE regulated the PI3K/AKT/mTOR pathway in TSCC cells. Additionally, high levels of CRNDE inhibited tumor growth in vivo. In conclusion, high levels of CRNDE might promote TSCC progression at least partly through regulating the PI3K/AKT/mTOR pathway. Targeting CRNDE has potential to be used as a novel target of TSCC treatment.

The long non-coding RNA CRNDE competed endogenously with miR-205 to promote proliferation and metastasis of melanoma cells by targeting CCL18

ABSTRACTMelanoma was the most malignant skin neoplasm with an increasing morbidity around the world. Although new immunotherapies and targeted therapies have emerged recently, the long-term survival of melanoma patients still remains low. To reveal effective diagnostic methods and therapeutic strategies, the potential mechanism of melanoma is urgently needed to be studied. Long non-coding RNAs (lncRNAs) have become an important regulatory factor in the occurrence and development of cancer, and it can be used as a new prognostic and diagnostic marker. In this study, we aimed to inspect the effects of lncRNA colorectal neoplasia differentially expressed (CRNDE) on the melanoma cell viability, invasion and migration. After microarray analysis, 106 dysregulated lncRNAs and 1187 abnormally expressed mRNAs were screened out. Further, the lncRNA CRNDE and CCL18 expression in melanoma tissues and cell lines were examined. It was determined that they were both overexpressed in melanoma tissues and cell lines. The down-regulation of lncRNA CRNDE and CCL18 induced melanoma cell apoptosis and inhibited cell viability. Then, miR-205 which had binding site with lncRNA CRNDE and CCL18 was involved in the next experiment, and it was down-regulated in melanoma that negatively correlated with lncRNA CRNDE expression. In addition, overexpression of miR-205 results in the restore of cell viability and aggressiveness. In conclusion, LncRNA CRNDE promotes the migration and invasion of melanoma by sponging miR-205 and releasing CCL18.

CRNDE: An important oncogenic long non-coding RNA in human cancers.

Aberrant overexpression of long non-coding RNA CRNDE (Colorectal Neoplasia Differentially Expressed) is confirmed in various human cancers, which is correlated with advanced clinicopathological features and poor prognosis. CRNDE promotes cancer cell proliferation, migration and invasion, and suppresses apoptosis in complicated mechanisms, which result in the initialization and development of human cancers. In this review, we provide an overview of the oncogenic role and potential clinical applications of CRNDE.

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.

The long non-coding RNA CRNDE acts as a ceRNA and promotes glioma malignancy by preventing miR-136-5p-mediated downregulation of Bcl-2 and Wnt2.

The colorectal neoplasia differentially expressed (CRNDE) gene encodes a long non-coding RNA (lncRNA) that is the most unregulated among 129 lncRNAs differentially expressed in gliomas. In this study, we confirmed high CRNDE expression in clinical glioma specimens and observed through experiments in human glioma cell lines a novel molecular mechanism by which CRNDE may contribute to glioma pathogenesis. By inducing or silencing CRNDE expression, we detected a positive correlation between CRNDE levels and the proliferative, migratory, and invasive capacities of glioma cells, which were concomitant with a decreased apoptosis rate. Our experiments also suggest that these effects are mediated by downregulation of miR-136-5p, which correlated with the glioma WHO grade. Based on predicted CRNDE/miR-136-5p/mRNA interactions, both the mRNA and protein expression analyses suggested that miR-136-5p-mediated repression of Bcl-2 and Wnt2 underlies the pro-tumoral actions of CRNDE. We therefore propose that CRNDE functions as a competing endogenous RNA (ceRNA) that binds to and negatively regulates miR-136-5p, thereby protecting Bcl-2 and Wnt2 from miR-136-5p-mediated inhibition in glioma.