A novel lncRNA NR4A1AS upregulates orphan nuclear receptor NR4A1 expression by blocking UPF1-mediated mRNA destabilization in colorectal cancer

Long non-coding RNAs (lncRNAs) play important roles in tumorigenesis and cancer progression. The orphan nuclear receptor NR4A1 acts as an oncogene, and is involved in colorectal cancer (CRC) development. However, the mechanism through which lncRNA regulates NR4A1 expression remains unknown. We aimed to identify lncRNAs that regulate NR4A1 and assess their underlying mechanisms in CRC. We first identified an antisense lncRNA of NR4A1 that was upregulated in CRC tissues and cells with rapid amplification of cDNA ends, and designated it as NR4A1AS. Spearman correlation analysis showed that NR4A1AS was positively correlated with NR4A1 mRNA levels in 37 CRC tissues. Mechanistically, NR4A1AS stabilized NR4A1 mRNA by forming RNA-RNA complexes via partial base-pairing and upregulated NR4A1 expression in CRC cells. RNA immunoprecipitation assays revealed that knockdown of NR4A1AS expression by siRNA enhanced UPF1 recruitment to NR4A1 mRNA, thereby decreasing NR4A1 mRNA stability. Moreover, depletion of NR4A1AS was found to mimic the effect of NR4A1 knockdown, specifically by suppressing cell proliferation, migration and invasion, and inducing apoptosis and cell cycle arrest. Accordingly, restoring NR4A1 expression ameliorated the effects of NR4A1AS knockdown on tumor growth and metastasis of CRC cells in vitro and in vivo . Thus, we conclude that NR4A1AS upregulates NR4A1 expression by forming RNA-RNA complexes and blocking UPF1-mediated mRNA destabilization, and it functions in tumor...
Source: Clinical Science - Category: Biomedical Science Authors: Tags: PublishAheadOfPrint Source Type: research

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CONCLUSIONS The findings supported that hsa_circ_0079993 acts as an oncogene in CRC through the miRNA-203a-3p.1/CREB1 axis. PMID: 31515467 [PubMed - in process]
Source: Medical Science Monitor - Category: Research Tags: Med Sci Monit Source Type: research
Authors: Meng H, Wu J, Huang Q, Yang X, Yang K, Qiu Y, Ren J, Shen R, Qi H Abstract Neural precursor cell-expressed, developmentally-downregulated 9 (NEDD9) is a multi-domain skeleton protein that serves an important role in the cell signaling process via modulating invasion, metastasis, proliferation and apoptosis of tumor cells. The present study identified that the expression levels of NEDD9 in colorectal cancer were elevated. Therefore, the effect of downregulating the expression of NEDD9 in terms of invasion and migration of colorectal cancer cells was investigated and the role of the JNK pathway in these proc...
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
Authors: Zheng K, Yang Q, Xie L, Qiu Z, Huang Y, Lin Y, Tu L, Cui C Abstract Tumor metastasis and anticancer drug resistance are the major causes of mortality in patients with colorectal cancer (CRC). Due to the limitations of conventional biomarkers, it is urgent to identify novel and valid biomarkers to predict the progression and prognosis of CRC. Reverse transcription-quantitative polymerase chain reaction and western blotting were used to detect MAGT1 expression in CRC clinical samples or cell lines. Bioinformatics analysis was used to investigate the association between MAGT1 alteration and clinicopathologica...
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
In conclusion, the findings provided novel approaches for the identification of β-catenin targets, which may become prognostic biomarkers or drug targets for the management of CRC. PMID: 31516589 [PubMed]
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
Authors: Zhou W, Pan B, Liu L Abstract The aberrant expression of long non-coding RNAs (lncRNAs) has been associated with a variety of malignancies, including colorectal cancer (CRC); however, the key lncRNAs associated with patient prognosis and their biological roles in CRC are yet to be determined. The aim of the present study was to determine the key lncRNAs associated with patient prognosis as well as their biological roles in CRC. Therefore, a dataset from The Cancer Genome Atlas containing the lncRNA expression data of 521 CRC and normal colorectal mucosal tissues, as well as the corresponding clinical data,...
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
Authors: Yu J, Xie Y, Li M, Zhou F, Zhong Z, Liu Y, Wang F, Qi J Abstract Abnormal methylation of secreted frizzled-related proteins (SFRPs) has been observed in various human cancer types. The loss of SFRP gene expression induces the activation of the Wnt pathway and is a vital mechanism for tumorigenesis and development. The aim of the present systematic review was to assess the association between SFRP methylation and cancer risk. A meta-analysis was systematically conducted to assess the clinicopathological significance of SFRP methylation in cancer risk. The Cochrane Library, PubMed and Web of Science database...
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
Authors: Mendoza-Almanza G, Ortíz-Sánchez E, Rocha-Zavaleta L, Rivas-Santiago C, Esparza-Ibarra E, Olmos J Abstract Cervical cancer (CC) is one of the leading causes of cancer-associated mortalities in women from developing countries. Similar to other types of cancer, CC is considered to be a multifactorial disease, involving socioeconomic, cultural, immunological and epigenetic factors, as well as persistent human papilloma virus (HPV) infection. It has been well established that cancer stem cells (CSCs) play an important role in defining tumor size, the speed of development and the level of regressi...
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
Conclusion: The combination of 2-DG and photon therapy, as well as irradiation with carbon ions can overcome radioresistance of tumor cells such as WiDr. PMID: 31517070 [PubMed]
Source: Clinical Colorectal Cancer - Category: Cancer & Oncology Authors: Tags: Clin Transl Radiat Oncol Source Type: research
ConclusionFurther studies should be conducted to provide new insights about survival of colorectal carcinoma in Lynch syndrome, as well as the therapeutic alternatives for this neoplasia.ResumoIntroduçãoO carcinoma colorretal é a terceira neoplasia mais prevalente no mundo, bem como a segunda causa de morte por câncer. A maioria destas neoplasias são esporádicas, devidas a mutações somáticas, mas cerca de 15% são hereditárias como a síndrome de Lynch ou Hereditary Nonpolyposis Colorectal Cancer (HNPCC). Apesar de ser a mesma neoplasia, esta ...
Source: Journal of Coloproctology - Category: Gastroenterology Source Type: research
This study aimed to determine the associations between asbestos exposure and colorectal cancer. We performed a meta-analysis to quantitatively evaluate this association. A fixed effects model was used to summarize the relative risks across studies. Sources of heterogeneity were explored through subgroup analyses and meta-regression. We analyzed the dose-effect relationship using lung cancer Standardized mortality ratio (SMR) and the risk of mesothelioma as a percent (%) as exposure surrogates. A total of 47 cohort studies were included. We identified 28 incidence cohort studies from 17 separate papers and extracted colorec...
Source: Industrial Health - Category: Occupational Health Tags: Ind Health Source Type: research
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