The Clinical Significance of CRNDE Gene Methylation, Polymorphisms, and CRNDEP Micropeptide Expression in Ovarian Tumors
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PROVIDER: PRJNA1093143 | ENA |
REPOSITORIES: ENA
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Project description:Abstract: CRNDE is an oncogene expressed as a long non-coding RNA. However, our team previously reported that the CRNDE gene also encodes a micropeptide, CRNDEP. The amino acid sequence of CRNDEP has recently been revealed by other researchers, too. This study aimed to investigate genetic alterations within the CRNDEP-coding region of the CRNDE gene, methylation profiling of this gene, and CRNDEP expression analysis. All investigations were performed on clinical material from patients with ovarian tumors of diverse aggressiveness. We found that CRNDEP levels were significantly elevated in highly aggressive tumors compared to benign neoplasms. Consistently, a high level of this micropeptide was a negative, independent, prognostic, and predictive factor in high-grade ovarian cancer (hgOvCa) patients. The cancer-promoting role of CRNDE(P), shown in our recent study, was also supported by genetic and epigenetic results obtained herein, revealing no CRNDEP-disrupting mutations in any clinical sample. Moreover, in borderline ovarian tumors (BOTS), but not in ovarian cancers, the presence of a single nucleotide polymorphism in CRNDE, rs115515594, significantly increased the risk of recurrence. Consistently, in BOTS only, the same genetic variant was highly overrepresented compared to healthy individuals. We also discovered that hypomethylation of CRNDE is associated with increased aggressiveness of ovarian tumors. Accordingly, hypomethylation of this gene’s promoter/first exon correlated with hgOvCa resistance to chemotherapy, but only in specimens with accumulation of the TP53 tumor suppressor protein. Taken together, these results contribute to a better understanding of the role of CRNDE(P) in tumorigenesis and potentially may lead to improvements in screening, diagnosis, and treatment of ovarian neoplasms.
2024-07-27 | GSE262765 | GEO
Project description:Abstract: CRNDE is considered an oncogene expressed as long non-coding RNA. Our previous paper is the only one reporting CRNDE as a micropeptide-coding gene. The amino acid sequence of this micropeptide (CRNDEP) has recently been confirmed by other researchers. This study aimed at the mass spectrometry(MS)-based validation of the CRNDEP sequence and investigation of how the differential expression of CRNDE(P) influences the metabolism and chemoresistance of ovarian cancer (OvCa) cells. We also assessed cellular localization changes of CRNDEP, looked for its protein partners, and bioinformatically evaluated its RNA-binding capacities. Herein, we detected most of the CRNDEP sequence by MS. Moreover, our results corroborated the oncogenic role of CRNDE, portraying it as the gene impacting carcinogenesis at the stages of DNA transcription and replication, affecting the RNA metabolism, and stimulating the cell cycle progression and proliferation, with CRNDEP being detected in the centrosomes of dividing cells. We also showed that CRNDEP is located in nucleoli, and revealed interactions of this micropeptide with p54, an RNA helicase. Besides, we proved the high CRNDE(P) expression to increase the resistance of OvCa cells to treatment with microtubule-targeted cytostatics. Furthermore, altered CRNDE(P) expression affected the activity of the microtubular cytoskeleton and the formation of focal adhesion plaques. Finally, according to our in silico analyses, CRNDEP is likely capable of RNA binding. All these results contribute to a better understanding of the CRNDE(P) role in OvCa biology, which may potentially improve screening, diagnosis, and treatment of this disease.
2024-04-28 | PXD044160 | Pride
Project description:To identify the genes targeted by CRNDE and explore the mechanism of action of CRNDE on CRC tumorigenesis, gene expression profiling was performed on CRNDE knockdown DLD1 cells s and on control cells.
2017-09-06 | GSE89985 | GEO
Project description: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.
2020-09-04 | GSE155091 | GEO
Project description:Abstract: CRNDE is considered an oncogene expressed as long non-coding RNA. Our previous paper is the only one reporting CRNDE as a micropeptide-coding gene. The amino acid sequence of this micropeptide (CRNDEP) has recently been confirmed by other researchers. This study aimed at the mass spectrometry(MS)-based validation of the CRNDEP sequence and investigation of how the differential expression of CRNDE(P) influences the metabolism and chemoresistance of ovarian cancer (OvCa) cells. We also assessed cellular localization changes of CRNDEP, looked for its protein partners, and bioinformatically evaluated its RNA-binding capacities. Herein, we detected most of the CRNDEP sequence by MS. Moreover, our results corroborated the oncogenic role of CRNDE, portraying it as the gene impacting carcinogenesis at the stages of DNA transcription and replication, affecting the RNA metabolism, and stimulating the cell cycle progression and proliferation, with CRNDEP being detected in the centrosomes of dividing cells. We also showed that CRNDEP is located in nucleoli, and revealed interactions of this micropeptide with p54, an RNA helicase. Besides, we proved the high CRNDE(P) expression to increase the resistance of OvCa cells to treatment with microtubule-targeted cytostatics. Furthermore, altered CRNDE(P) expression affected the activity of the microtubular cytoskeleton and the formation of focal adhesion plaques. Finally, according to our in silico analyses, CRNDEP is likely capable of RNA binding. All these results contribute to a better understanding of the CRNDE(P) role in OvCa biology, which may potentially improve screening, diagnosis, and treatment of this disease.
2024-04-28 | PXD044196 | Pride
Project description:Introduction: Overcoming of acquired resistance to EGFR-tyrosine kinase inhibitors (EGFR-TKIs) is an intractable obstacle for many clinical oncologists. The mechanisms of resistance to EGFR-TKIs are very 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 largely unknown. Methods: Osimertinib and afatinib-resistant EGFR-mutated lung cancer cells were established using by a stepwise method. Microarray analysis of non-coding and coding RNAs was performed using parental and resistant EGFR-mutant NSCLC cells. Results: Microarray analysis was evaluated by bioinformatics analysis through medical-industrial collaboration. CRNDE and DGCR5 lncRNAs were highly expressed in EGFR-TKIs-resistant cells. CRNDE binds to eIF4A3 protein, down-regulates eIF4A3 and MUC1 expression, and down-regulates p-EGFR expression. CRNDE inhibition activated the eIF4A3/MUC1/EGFR signaling pathway and apoptotic activity and restored sensitivity to EGFR-TKIs. Conclusions: We identified lncRNA CRNDE associated with resistance to EGFR-TKIs in EGFR-mutant NSCLC cells. CRNDE may be a novel therapeutic target for EGFR mutant NSCLC patients.
2021-04-28 | GSE163913 | GEO
Project description:The expression and clinical significance of stomatin-like protein 2 (SLP-2) in ovarian tumors were investigated. A total of 280 cases of ovarian tissue specimens preserved from inpatients after surgical treatments in the Department of Oncology of Yidu Central Hospital of Weifang from April 2013 to May 2016 were collected, including 130 cases of malignant ovarian tumor tissue specimens (malignant tumor group), 75 cases of benign ovarian tumor tissue specimens (benign tumor group) and 75 cases of normal ovarian tissue specimens from bilateral ovariectomy for unilateral ovarian lesions (control group). Immunohistochemistry was used to detect the expression of SLP-2 protein in the three groups. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was utilized to detect the relative expression of SLP-2 mRNA in the three groups, and the relationship between SLP-2 and clinicopathological parameters of the ovarian cancer patients was analyzed. The patients with ovarian cancer were divided into the SLP-2 high-expression group and the SLP-2 low-expression group according to the median of SLP-2 relative expression. The survival of patients was analyzed using the Kaplan-Meier and Cox regression model. The results of immunohistochemistry showed that the positive expression rate of SLP-2 protein in the malignant tumor group was significantly higher than that in the benign tumor and control groups (P<0.001). The results of RT-qPCR showed that compared with the control group, the relative expression of SLP-2 mRNA in the ovarian tissues in the benign tumor group and the malignant tumor group was increased (P<0.001). The relative expression of SLP-2 mRNA in the malignant tumor group was higher than that in the benign tumor group (P<0.001). The relative expression of SLP-2 mRNA correlated with clinical stage, pathological differentiation and lymph node metastasis of the patients with ovarian cancer (P<0.05). The 5-year overall survival (OS) in the SLP-2 mRNA high expression group was significantly lower than that in the SLP-2 mRNA low expression group at 5 years (P<0.05). SLP-2 mRNA was an independent prognostic factor influencing OS of the patients (P<0.05). SLP-2 may be involved in the occurrence and development of ovarian cancer and related to the clinical stage, pathological differentiation and lymph node metastasis of the patients with ovarian cancer, which may also play a role in promoting the invasion and metastasis processes of ovarian cancer. Therefore, SLP-2 is expected to be an effective biomarker for targeted treatment and prognosis of ovarian tumor.
| S-EPMC6444406 | biostudies-literature
Project description: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. In addition, 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 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.
2019-12-20 | GSE141126 | GEO
Project description:We found gene expression profiling of spheroid-forming cell (cancer stem-like cell) by cDNA microarray and validated the genes as prognostic markers of ovarian serous carcinoma.
2014-08-27 | GSE60765 | GEO
Project description:The distinction between primary and secondary ovarian tumors may be challenging for pathologists. We performed transcriptomic analysis in order to discriminate between primary ovarian tumors and ovarian metastases after primary breast cancer. We performed genomic analysis on tumor paired samples (breast/ovary) in order to know if genomic profiles could help for the discrimination of primary ovarian tumors and ovarian metastases after primary breast cancer.
2010-04-14 | GSE20565 | GEO