Colorectal Neoplasia Differentially Expressed Research Articles

CRNDE: A Pivotal Oncogenic Long Non-Coding RNA in Cancers.

Colorectal Neoplasia Differentially Expressed (CRNDE), a long non-coding RNA that was initially identified as aberrantly expressed in colorectal cancer (CRC) has also been observed to exhibit elevated expression in various other human malignancies. Recent research has accumulated substantial evidence implicating CRNDE as an oncogenic player, exerting influence over critical cellular processes linked to cancer progression. Particularly, its regulatory interactions with microRNAs and proteins have been shown to modulate pathways that contribute to carcinogenesis and tumorigenesis. This review will comprehensively outline the roles of CRNDE in colorectal, liver, glioma, lung, cervical, gastric and prostate cancer, elucidating the mechanisms involved in modulating proliferation, apoptosis, migration, invasion, angiogenesis, and radio/chemoresistance. Furthermore, the review highlights CRNDE's potential as a multifaceted biomarker, owing to its presence in diverse biological samples and stable properties, thereby underscoring its diagnostic, therapeutic, and prognostic applications. This review aims to provide comprehensive insights of CRNDE-mediated oncogenesis and identify CRNDE as a promising target for future clinical interventions.

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 mediated hnRNPA2B1 stability facilitates nuclear export and translation of KRAS in colorectal cancer

Development of colorectal cancer (CRC) involves activation of Kirsten rat sarcoma viral oncogene homolog (KRAS) signaling. However, the post-transcriptional regulation of KRAS has yet to be fully characterized. Here, we found that the colorectal neoplasia differentially expressed (CRNDE)/heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2B1) axis was notably elevated in CRC and was strongly associated with poor prognosis of patients, while also significantly promoting CRC cell proliferation and metastasis both in vitro and in vivo. Furthermore, CRNDE maintained the stability of hnRNPA2B1 protein by inhibiting E3 ubiquitin ligase TRIM21 mediated K63 ubiquitination-dependent protein degradation. CRNDE/hnRNPA2B1 axis facilitated the nuclear export and translation of KRAS mRNA, which specifically activated the MAPK signaling pathway, eventually accelerating the malignant progression of CRC. Our findings provided insight into the regulatory network for stable hnRNPA2B1 protein expression, and the molecular mechanisms by which the CRNDE/hnRNPA2B1 axis mediated KRAS nucleocytoplasmic transport and translation, deeply underscoring the bright future of hnRNPA2B1 as a promising biomarker and therapeutic target for CRC.By hindering hnRNPA2B1 from binding to the E3 ubiquitin ligase TRIM21, whose mediated ubiquitin-dependent degradation was thereby inhibited, CRNDE protected the stability of hnRNPA2B1’s high protein expression in CRC. Supported by the high level of the oncogenic molecule CRNDE, hnRNPA2B1 bound to KRAS mRNA and promoted KRAS mRNA nucleus export to enter the ribosomal translation program, subsequently activating the MAPK signaling pathway and ultimately accelerating the malignant progression of CRC.

Autophagy in combination therapy of temozolomide and IFN-γ in C6-induced glioblastoma: role of non-coding RNAs.

Aim: We predicted the modulation of autophagy and apoptosis in response to temozolomide (TMZ) and IFN-γbased on changes in the expression of non-coding RNAs in C6-induced glioblastoma (GBM). Materials & methods: Each rat received an intraperitoneal injection of TMZ (7.5mg/kg)and/or IFN-γ (50,000IU). Results: The reduced expression of H19 and colorectal neoplasia differentially expressed (CRNDE) was associated with a reduction in autophagy in response to TMZ, IFN-γand TMZ+IFN-γ therapy, whereas the decreased level of miR-29a (proapoptotic miRNA) was associated with an increase in apoptosis. Conclusion: It appears that H19 promotes switching from autophagy to apoptosis in response to combination therapy of TMZ and IFN-γ through the miR-29a/autophagy-related protein 9A (ATG9A) pathway in C6-induced GBM.

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.

CRNDE acts as an epigenetic modulator of the p300/YY1 complex to promote HCC progression and therapeutic resistance

BackgroundHepatocellular carcinoma (HCC) is one of the most common primary liver malignancies worldwide. The long-term prognosis for HCC remains extremely poor, with drug resistance being the major underlying cause of recurrence and mortality. The lncRNA colorectal neoplasia differentially expressed (CRNDE) is an epigenetic mediator and plays an important role to drive proliferation and drug resistance in HCC. However, CRNDE as an epigenetic regulator with influences sorafenib resistance in HCC is unclear. Thus, we explore the potential of targeting the CRNDE/p300/YY1 axis as a novel therapeutic strategy to overcome sorafenib resistance of HCC.MethodDetection of the expression level of CRNDE and EGFR in clinical specimens of HCC. CRNDE, EGFR, p300, and YY1expression were altered in HCC cells through transfection with different plasmids, and cell proliferation, migration, invasion, and sorafenib resistance were subsequently observed. Immunoprecipitation, chromatin immunoprecipitation, re-chromatin immunoprecipitation, site-directed mutagenesis, RNA Immunoprecipitation, immune fluorescence, qRT-PCR, and western blotting were performed to uncover the mechanisms of CRNDE regulation. The xenograft nude mice model was used to investigate the tumor growth and sorafenib resistance.ResultsIn this study, we showed that CRNDE expression is significantly positively correlated with that of epidermal growth factor receptor (EGFR) in clinical specimens of HCC and induces proliferation and sorafenib resistance of HCC via EGFR-mediated signaling. Mechanistically, CRNDE stabilized the p300/YY1 complex at the EGFR promoter and simultaneously enhanced histone H3K9 and H3K27 acetylation, which serve as markers of relaxed chromatin. EGFR was positively upregulated by the epigenetic complex, p300/YY1, in a manner dependent on CRNDE expression, leading to enhanced tumor cell proliferation and sorafenib resistance. Furthermore, C646, a p300 inhibitor, suppressed EGFR transcriptional activity by decreasing chromatin relaxation and YY1 binding, which effectively reduced proliferation/sorafenib resistance and prolonged overall survival.ConclusionOur collective findings support the potential of targeting the CRNDE/p300/YY1 axis as a novel therapeutic strategy to overcome sorafenib resistance of HCC.

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.

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.

LncRNA CRNDE hinders the progression of osteoarthritis by epigenetic regulation of DACT1.

Osteoarthritis (OA) is mainly characterized by articular cartilage degeneration, synovial fibrosis, and inflammation. LncRNA CRNDE (colorectal neoplasia differentially expressed) has been reported to be down-regulated in age-related OA, but its role in injury-induced OA needs to be further explored. In this study, an OA rat model was established using anterior cruciate ligament transection, and the adenovirus-mediated CRNDE overexpression (Ad-CRNDE) or DACT1 (dapper antagonist of catenin-1) interference (sh-DACT1) vectors were administered by intraarticular injection. Moreover, chondrocyte‑like ATDC5 cells were treated with IL-1β (10ng/mL) to simulate OA conditions in vitro. We found that overexpression of CRNDE alleviated cartilage damage and synovitis in OA rats, and suppressed IL-1β-induced apoptosis, inflammation, and extracellular matrix (ECM) degradation in chondrocyte‑like ATDC5 cells, while silencing DACT1 effectively antagonized the protective effect of CRNDE both in vivo and in vitro. Mechanism studies revealed that DACT1 could act as a downstream target of CRNDE. By recruiting p300, CRNDE promoted the enrichment of H3K27ac in the DACT1 promoter, thus promoting DACT1 transcription. In addition, CRNDE hindered the activation of the Wnt/β-catenin pathway in IL-1β-stimulated cells by inducing DACT1 expression. In conclusion, CRNDE promoted DACT1 expression through epigenetic modification and restrained the activation of Wnt/β-catenin signaling to impede the progression of OA.

Development and validation of a prediction model for metastasis in colorectal cancer based on LncRNA CRNDE and radiomics

Accurate prediction of metastasis is an important determinant for selecting appropriate treatment for advanced colorectal cancer (CRC). In this study, 1250 patients in two hospitals from 2014 to 2019 histologically diagnosed with CRC were enrolled. We performed the transcriptome analysis on 141 CRC patients. RNA-seq analysis revealed that long noncoding RNA (LncRNA) colorectal neoplasia differentially expressed (CRNDE) played an important role in CRC metastasis. The least absolute shrinkage and selection operator regression was used to select features and develop radiomics model. Multivariate logistic regression analysis was used to develop combined model. The radiomics model with 13 filtered radiomics features had good discrimination in predicting expression level of LncRNA CRNDE in training set (receiver operating characteristic [AUC] = 0.809) and testing set (AUC = 0.755). Furthermore, the radiomics model could predict the metastasis of CRC in internal validation set (AUC, 0.665) and in external validation set (AUC = 0.690). The combined model developed with radiomics score and carcinoembryonic antigen had better performance, and the AUC was 0.708, 0.700 in internal validation set and in external validation set, respectively. In conclusion, we proposed a radiomics model and combined model, which could predict the expression level of LncRNA CRNDE and further predict CRC metastasis, thereby helping clinician make treatment decisions.

Expression of colorectal neoplasia differentially expressed in anaplastic thyroid carcinoma and its effect on cancer cell proliferation.

BackgroundThe incidence of anaplastic thyroid cancer (ATC) is high among human cancers. Colorectal neoplasia differentially expressed (CRNDE) is highly expressed in common tumors, and is therefore a potential molecular target for anti-tumor therapy. However, the function of CRNDE in ATC remains elusive.MethodsThe Gene Expression Omnibus (GEO) database was used to screen the differential expression of long-noncoding RNA (lncRNA) in ATC tissues. The Cancer Genome Atlas (TCGA) database was used to analyze the expression of CRNDE in thyroid cancer (THCA) tissues and its impact on patient prognosis. Quantitative real-time PCR (qRT-PCR) was used to determine the expression level of CRNDE in tumor and control tissues. The biological function of CRNDE in THCA was explored using TCGA RNA sequencing (RNA-seq) data analysis. ATC cell lines with low and high CRNDE expression were selected for CRNDE siRNA transfection, and the proliferation of cells was detected in each group.ResultsThe GEO and TCGA databases analysis results showed that CRNDE was highly expressed in ATC tissues, which is related to the poor prognosis of THCA patients. Also, the expression of CRNDE in the ATC cell line, ARO (human thyroid cancer cell line), was relatively high, while the expression in sw579 is relatively low. Therefore, ARO and sw579 were chosen for CRNDE small interfering RNA (siRNA) transfection. Compared with negative control (si-NC), the expression of CRNDE in si-CRNDE-1, si-CRNDE-2, and si-CRNDE-3 was reduced, indicating that the inhibitory effect was significantly enhanced and the cell proliferation ability was reduced, and the cell cycle is arrested in the G0/G1 phase. Finally, it was found that the wnt3a, β-catenin, and cyclinD1 protein expressions of si-CRNDE-1 and si-CRNDE-2 were significantly reduced.ConclusionsThe high expression of CRNDE in ATC tissues may promote the proliferation of ATC cells by regulating the Wnt/β-catenin signaling pathway. CRNDE may be a potential molecular target for the treatment of ATC.

Long non-coding RNA metastasis-related lung adenocarcinoma transcript 1 (MALAT1) forms a negative feedback loop with long non-coding RNA colorectal neoplasia differentially expressed (CRNDE) in sepsis to regulate lung cell apoptosis

ABSTRACT It has been reported that long non-coding RNAs (lncRNAs) metastasis-related lung adenocarcinoma transcript 1 (MALAT1) and colorectal neoplasia differentially expressed (CRNDE) play opposite roles in sepsis. Therefore, we explored their potential interaction with sepsis. To this end, we determined MALAT1 and CRNDE levels using RT-qPCR in plasma samples collected from healthy controls (n = 60) and sepsis patients (n = 60) before and after treatment and the effects of MALAT1 and CRNDE overexpression in human bronchial epithelial cells (HBEpCs) on the expression of each other and HBEpC apoptosis. RT-qPCR analyses showed that MALAT1 was upregulated, while CRNDE was downregulated in sepsis and overexpression of MALAT1 and CRNDE downregulated the expression of each other. After proper treatment, MALAT1 was downregulated and CRNDE was upregulated in sepsis. Lipopolysaccharides (LPS) treatment of HBEpCs upregulated MALAT1 and downregulated CRNDE. Cell apoptosis analysis showed that MALAT1 overexpression promoted, while CRNDE overexpression inhibited LPS-induced HBEpC apoptosis. Moreover, CRNDE overexpression attenuated the effects of MALAT1 overexpression. Overall, MALAT1 might form a negative feedback loop with CRNDE in sepsis to regulate lung cell apoptosis.

Construction of ceRNA networks with different types of IDH1 mutation status in low-grade glioma patients

BackgroundIsocitrate dehydrogenase 1 (IDH1) mutation status is related to the prognosis and immune microenvironment of glioma. Long non-coding ribonucleic acids (lncRNAs) interact with microRNAs (miRNAs), and play roles in the competitive endogenous RNA (ceRNA) network and tumor progression.MethodsData on low-grade glioma (LGG) IDH1 mutation was acquired from The Cancer Genome Atlas (TCGA). An empirical analysis of differential gene expression was conducted to identify differentially expressed mRNAs (DEmRNAs), differentially expressed miRNAs (DEmiRNAs), and differentially expressed lncRNAs (DElncRNAs). Survival-associated genes were identified by a univariate Cox regression analysis. An enrichment analysis was conducted to explore the gene ontology and pathways of the DEmRNAs.ResultsEighty-eight DEIDH1mRNAs, 88 DEIDH1lncRNAs, and 6 DEIDH1miRNAs were identified to construct a ceRNA network of LGG patients. Validated by Chinese Glioma Genome Atlas and our LGG patients of gene expression and survival, and the colorectal neoplasia differentially expressed (CRNDE), HOXA transcript antisense RNA, myeloid-specific 1 (HOTAIRM1)/miRNA-206a/hepatocyte nuclear factor 4 (HNF4G) axis was determined.ConclusionsWe established a ceRNA network by integrating the different IDH1 mutation statuses of LGG patients, and identified HNF4G, CRNDE, and HOTAIRM1 as genes related to the prognosis of and immune infiltration in LGG patients. Our findings suggest that these genes may be targets for LGG treatment, especially for patients with the wild-type IDH1 gene variants.

CRNDE silencing promotes apoptosis and enhances cisplatin sensitivity of colorectal carcinoma cells by inhibiting the Akt/mTORC1-mediated Warburg effect.

Colorectal cancer (CRC) is one of the most prevalent gastrointestinal tumors worldwide, with a high mortality rate. The lncRNA colorectal neoplasia differentially expressed (CRNDE) is upregulated in CRC and is involved in regulating the apoptosis, proliferation, and drug sensitivity of CRC cells. However, the specific underlying mechanisms remain to be elucidated. The aim of the present study was to investigate the effects of CRNDE on the Warburg effect in CRC cells, as well as the associated mechanisms. The expression of CRNDE in HCT-116 cells was overexpressed or silenced by transfection. Apoptosis, cisplatin sensitivity, the Warburg effect, and Akt/mTOR activation were evaluated. The results demonstrated that CRNDE inhibition decreased the proliferation and increased the apoptosis and cisplatin sensitivity of HCT-116 cells. In addition, CRNDE inhibition attenuated the Warburg effect in HCT-116 cells, as verified by a decrease in ATP production, lactic acid levels, glucose uptake, and the expression of Warburg effect-related enzymes (GLUT1, LDHA, HK2, and PKM2). CRNDE inhibition also suppressed the activity of the Akt/mTORC1 pathway, as demonstrated by the decreased phosphorylation of Akt, S6K, S6, and mTOR and the increased phosphorylation of 4EBP-1 and EIF-4E. The CRNDE overexpression-induced increase in ATP and lactic acid levels and glucose uptake in HCT-116 cells was reversed by Akt and mTOR inhibitors. These findings indicate that CRNDE silencing promotes apoptosis and enhances cisplatin sensitivity in colorectal carcinoma cells, which may be mediated by the regulation of the Warburg effect via the Akt/mTORC1 pathway. The present study thus provides a potential strategy for the treatment of CRC.

LncRNA colorectal neoplasia differentially expressed exacerbates the impairments in learning and memory induced by isoflurane.

This observation aimed to investigate the effect of colorectal neoplasia differentially expressed (CRNDE) targeted miR-212-5p on cognitive impairment induced by isoflurane (ISO) anesthesia in rats. The cognitive function of rats was measured by Morris water maze test. QRT-PCR detection of CRNDE and miR-212-5p expression levels in rats in each group. Double luciferase was used to verify the targeting relationship between miR-212-5p and CRNDE, and commercial kits were used to detect the level of inflammatory cytokines in hippocampus. The concentration of CRNDE was enhanced in rats treated by ISO anesthetic. The neurological severity score was elevated, the escape latency of rats was prolonged, the stay time in the quadrant of the platform, and the number of times crossing the platform decreased in the ISO group. The above indexes of rats in ISO + si-CRNDE were improved. MiR-212-5p is a mediator in the management of CRNDE on cognition and inflammation. CRNDE led to the deterioration of impairment on cognition induced by ISO through suppressing miR-212-5p expression and promoting neuroinflammation.

LncRNA colorectal neoplasia differentially expressed promotes glycolysis of liver cancer cells by regulating hypoxia-inducible factor 1α.

LncRNAs are associated with tumorigenesis of liver cancer. LncRNA Colorectal Neoplasia Differentially Expressed (CRNDE) was identified as an oncogenic lncRNA and involved in tumor growth and metastasis. The role of CRNDE in liver cancer was investigated. CRNDE was elevated in liver cancer cells. Knockdown of CRNDE decreased cell viability and inhibited proliferation of liver cancer. Moreover, knockdown of CRNDE reduced levels of extracellular acidification rate, glucose consumption, and lactate production to repress glycolysis of liver cancer. Silence of CRNDE enhanced the expression of miR-142 and reduced enhancer of zeste homolog 2 (EZH2) and hypoxia-inducible factor 1α (HIF-1α). Over-expression of HIF-1α attenuated CRNDE silence-induced decrease of glucose consumption and lactate production. Injection with sh-CRNDE virus reduced in vivo tumor growth of liver cancer through up-regulation of miR-142 and down-regulation of EZH2 and HIF-1α. In conclusion, knockdown of CRNDE suppressed cell proliferation, glycolysis, and tumor growth of liver cancer through EZH2/miR-142/HIF-1α.

The lncRNA CRNDE is regulated by E2F6 and sensitizes gastric cancer cells to chemotherapy by inhibiting autophagy.

Chemotherapy is an important treatment for gastric cancer (GC), but the primary and secondary drug resistance of tumours to chemotherapy seriously affects its curative effect. In recent years, the relationship between long noncoding RNAs (lncRNAs) and malignant tumours has received increasing attention. Based on accumulating evidence, lncRNAs are involved in the chemoresistance of GC, but the underlying mechanisms remain unclear. In this study, we identified the lncRNA colorectal neoplasia differentially expressed (CRNDE) as an important regulator of autophagy-associated chemoresistance in GC. Mechanistically, overexpression of CRNDE inhibits autophagy and induces apoptosis, thereby sensitizing GC cells to chemotherapy drugs. Moreover, E2F6, a classical transcriptional inhibitor, is confirmed to be upregulated in GC and represses the expression of CRNDE. The E2F6-CRNDE axis is clinically related to chemoresistant GC and poor outcomes in patients with advanced GC. Our findings suggest that the E2F6-CRNDE axis is a viable therapeutic target to protect against chemoresistance in GC.

Long noncoding RNAs Colorectal Neoplasia Differentially Expressed and taurine-upregulated gene 1 are downregulated in sepsis and positively regulate each other to suppress the apoptosis of cardiomyocytes

ABSTRACT Long noncoding RNAs (lncRNAs) Colorectal Neoplasia Differentially Expressed (CRNDE) and taurine-upregulated gene 1 (TUG1) play similar roles in sepsis, indicating the existence of the crosstalk between them. Sepsis is a major cause of injuries in heart, which are related to high mortality rates. This study was therefore carried out to analyze the potential crosstalk between CRNDE and TUG1 in sepsis, with a focus on sepsis-induced cell apoptosis in heart. Expression of CRNDE and TUG1 was analyzed with RT-qPCR. Correlations between them were analyzed by Pearson’s correlation coefficient. CRNDE and TUG1 were overexpressed in cardiomyocytes to determine the relationship between them. The roles of CRNDE and TUG1 in regulating the apoptosis of cardiomyocytes were explored by cell apoptosis assay. We found that both CRNDE and TUG1 were downregulated in sepsis. In cardiomyocytes, LPS treatment resulted in the downregulation of CRNDE and TUG1. Overexpression of CRNDE and TUG1 in cardiomyocytes increased the expression levels of each other. Under lipopolysaccharide (LPS) treatment, decreased apoptosis rates of cardiomyocytes were observed after CRNDE and TUG1 overexpression. CRNDE and TUG1 co-overexpression showed a stronger effect. In conclusion, CRNDE and TUG1 are downregulated in sepsis and they positively regulate each other to suppress the apoptosis of cardiomyocytes.

LncRNA CRNDE Exacerbates IgA Nephropathy Progression by Promoting NLRP3 Inflammasome Activation in Macrophages

ABSTRACT Background Activation of NLRP3 inflammasome in macrophages contributes greatly to IgA nephropathy (IgAN) progression. This study intended to investigate the underlying mechanism of NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation in the development of IgAN. Methods We examined the expression levels of colorectal neoplasia differentially expressed (CRNDE), NLRP3 inflammasome-related proteins in peripheral blood mononuclear cells (PBMCs) and J774A.1 cells and detected inflammatory cytokine levels in the serum of IgAN patients and cell supernatants of in vitro IgAN model. RNA pull-down and RNA immunoprecipitation (RIP) experiments were conducted to evaluate the interaction between CRNDE and NLRP3. Then, the ubiquitin level of NLRP3 and its binding ability to TRIM family member 31 (TRIM31) were determined. Results Compared with the control group, the expressions of CRNDE and NLRP3 inflammasome-related proteins in PBMCs and J774A.1 cells and levels of IL-1β, TNF-α and IL-12 in serum of IgAN patients and cell supernatants of IgA-IC-induced J774A.1 cells were all increased. CRNDE silencing down-regulated NLRP3 inflammasome-related proteins and the levels of IL-1β, TNF-α and IL-12 in cell supernatants, while NLRP3 overexpression reversed these effects. Additionally, CRNDE could interact with NLRP3 and promote NLRP3 expression. Furthermore, inhibition of CRNDE reduced NLRP3 protein level and promoted TRIM31-mediated NLRP3 ubiquitination and degradation. Conclusion CRNDE exacerbates IgA nephropathy progression through restraining ubiquitination and degradation of NLRP3 and facilitating NLRP3 inflammasome activation in macrophages.