F. nucleatum targets lncRNA ENO1-IT1 to promote glycolysis and oncogenesis in colorectal cancer

Gut ◽  
2020 ◽  
pp. gutjnl-2020-322780
Author(s):  
Jie Hong ◽  
Fangfang Guo ◽  
Shi-Yuan Lu ◽  
Chaoqin Shen ◽  
Dan Ma ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Glucose Metabolism ◽  
Target Genes ◽  
Colorectal Carcinogenesis ◽  
Pcr Analysis ◽  
Positron Emission ◽  
Non Coding Rna ◽  
Cancer Models ◽  
Chromatin Immunoprecipitation Sequencing ◽  
Rna Immunoprecipitation

ObjectiveMicrobiota disorder promotes chronic inflammation and carcinogenesis. High glycolysis is associated with poor prognosis in patients with colorectal cancer (CRC). However, the potential correlation between the gut microbiota and glucose metabolism is unknown in CRC.Design18F-FDG (18F-fluorodeoxyglucose) PET (positron emission tomography)/CT image scanning data and microbiota PCR analysis were performed to measure the correlation between metabolic alterations and microbiota disorder in 33 patients with CRC. Multiple colorectal cancer models, metabolic analysis and Seahorse assay were established to assess the role of long non-coding RNA (lncRNA) enolase1-intronic transcript 1 (ENO1-IT1) in Fusobacterium (F.) nucleatum-induced glucose metabolism and colorectal carcinogenesis. RNA immunoprecipitation and chromatin immunoprecipitation sequencing were conducted to identify potential targets of lncRNA ENO1-IT1.ResultsWe have found F. nucleatum abundance correlated with high glucose metabolism in patients with CRC. Furthermore, F. nucleatum supported carcinogenesis via increasing CRC cell glucose metabolism. Mechanistically, F. nucleatum activated lncRNA ENO1-IT1 transcription via upregulating the binding efficiency of transcription factor SP1 to the promoter region of lncRNA ENO1-IT1. Elevated ENO1-IT behaved as a guider modular for KAT7 histone acetyltransferase, specifying the histone modification pattern on its target genes, including ENO1, and consequently altering CRC biological function.ConclusionF. nucleatum and glucose metabolism are mechanistically, biologically and clinically connected to CRC. Targeting ENO1 pathway may be meaningful in treating patients with CRC with elevated F. nucleatum.

scholarly journals Genetic Mutations and Non-Coding RNA-Based Epigenetic Alterations Mediating the Warburg Effect in Colorectal Carcinogenesis

Biology ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 847
Author(s):  
Batoul Abi Zamer ◽  
Wafaa Abumustafa ◽  
Mawieh Hamad ◽  
Azzam A. Maghazachi ◽  
Jibran Sualeh Muhammad
Keyword(s):  
Colorectal Cancer ◽  
Glucose Metabolism ◽  
Warburg Effect ◽  
Colorectal Carcinogenesis ◽  
Genetic Mutations ◽  
Epigenetic Alterations ◽  
Therapeutic Approaches ◽  
Non Coding Rna ◽  
Gradual Process ◽  
The Warburg Effect

Colorectal cancer (CRC) development is a gradual process defined by the accumulation of numerous genetic mutations and epigenetic alterations leading to the adenoma-carcinoma sequence. Despite significant advances in the diagnosis and treatment of CRC, it continues to be a leading cause of cancer-related deaths worldwide. Even in the presence of oxygen, CRC cells bypass oxidative phosphorylation to produce metabolites that enable them to proliferate and survive—a phenomenon known as the “Warburg effect”. Understanding the complex glucose metabolism in CRC cells may support the development of new diagnostic and therapeutic approaches. Here we discuss the most recent findings on genetic mutations and epigenetic modulations that may positively or negatively regulate the Warburg effect in CRC cells. We focus on the non-coding RNA (ncRNA)-based epigenetics, and we present a perspective on the therapeutic relevance of critical molecules and ncRNAs mediating the Warburg effect in CRC cells. All the relevant studies were identified and assessed according to the genes and enzymes mediating the Warburg effect. The findings summarized in this review should provide a better understanding of the relevance of genetic mutations and the ncRNA-based epigenetic alterations to CRC pathogenesis to help overcome chemoresistance.

scholarly journals Functional Analysis of Three miRNAs in Agropyron mongolicum Keng under Drought Stress

Agronomy ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 661 ◽  
Author(s):  
Xuting Zhang ◽  
Bobo Fan ◽  
Zhuo Yu ◽  
Lizhen Nie ◽  
Yan Zhao ◽  
...  
Keyword(s):  
Drought Stress ◽  
Drought Tolerance ◽  
High Throughput Sequencing ◽  
Target Genes ◽  
Northern China ◽  
Bioinformatic Analysis ◽  
Pcr Analysis ◽  
Rna Molecules ◽  
Natural Pasture ◽  
Non Coding Rna

Agropyron mongolicum Keng, a perennial diploid grass with high drought tolerance, belongs to the genus Agropyron, tribe Triticeae. It has made tremendous contributions toward reseeding natural pasture and seeding artificial grassland in China, especially in the arid and semi-arid area of northern China. As a wild relative of wheat, A. mongolicum is also a valuable resource for the genetic improvement of wheat crops. MicroRNAs are small non-coding RNA molecules ubiquitous in plants, which have been involved in responses to a wide variety of stresses including drought, salinity, chilling temperature. To date, little research has been done on drought-responsive miRNAs in A. mongolicum. In this study, two miRNA libraries of A. mongolicum under drought and normal conditions were constructed, and drought-responsive miRNAs were screened via Solexa high throughput sequencing and bioinformatic analysis. A total of 114 new miRNAs were identified in A. mongolicum including 53 conservative and 61 unconservative miRNAs, and 1393 target genes of 98 miRNAs were predicted. Seventeen miRNAs were found to be differentially expressed under drought stress, seven (amo-miR21, amo-miR62, amo-miR82, amo-miR5, amo-miR77, amo-miR44 and amo-miR17) of which were predicted to target on genes involved in drought tolerance. QRT-PCR analysis confirmed the expression changes of the seven drought related miRNAs in A. mongolicum. We then transformed the seven miRNAs into Arabidopsis thaliana plants, and three of them (amo-miR21, amo-miR5 and amo-miR62) were genetically stable. The three miRNAs demonstrated the same expression pattern in A. thaliana as that in A. mongolicum under drought stress. Findings from this study will better our understanding of the molecular mechanism of miRNAs in drought tolerance and promote molecular breeding of forage grass with improved adaption to drought.

scholarly journals Insulin-Like Growth Factor 1 (IGF-1) Signaling in Glucose Metabolism in Colorectal Cancer

2021 ◽  
Vol 22 (12) ◽  
pp. 6434
Author(s):  
Aldona Kasprzak
Keyword(s):  
Colorectal Cancer ◽  
Growth Factor ◽  
Glucose Metabolism ◽  
Warburg Effect ◽  
Mapk Signaling ◽  
Colorectal Carcinogenesis ◽  
Insulin Like Growth Factor ◽  
Aberrant Expression ◽  
The Warburg Effect

Colorectal cancer (CRC) is one of the most common aggressive carcinoma types worldwide, characterized by unfavorable curative effect and poor prognosis. Epidemiological data re-vealed that CRC risk is increased in patients with metabolic syndrome (MetS) and its serum components (e.g., hyperglycemia). High glycemic index diets, which chronically raise post-prandial blood glucose, may at least in part increase colon cancer risk via the insulin/insulin-like growth factor 1 (IGF-1) signaling pathway. However, the underlying mechanisms linking IGF-1 and MetS are still poorly understood. Hyperactivated glucose uptake and aerobic glycolysis (the Warburg effect) are considered as a one of six hallmarks of cancer, including CRC. However, the role of insulin/IGF-1 signaling during the acquisition of the Warburg metabolic phenotypes by CRC cells is still poorly understood. It most likely results from the interaction of multiple processes, directly or indirectly regulated by IGF-1, such as activation of PI3K/Akt/mTORC, and Raf/MAPK signaling pathways, activation of glucose transporters (e.g., GLUT1), activation of key glycolytic enzymes (e.g., LDHA, LDH5, HK II, and PFKFB3), aberrant expression of the oncogenes (e.g., MYC, and KRAS) and/or overexpression of signaling proteins (e.g., HIF-1, TGF-β1, PI3K, ERK, Akt, and mTOR). This review describes the role of IGF-1 in glucose metabolism in physiology and colorectal carcinogenesis, including the role of the insulin/IGF system in the Warburg effect. Furthermore, current therapeutic strategies aimed at repairing impaired glucose metabolism in CRC are indicated.

scholarly journals The LncRNA CASC11 Promotes Colorectal Cancer Cell Proliferation and Migration by Adsorbing miR-646 and miR-381-3p to Upregulate Their Target RAB11FIP2

2021 ◽  
Vol 11 ◽  
Author(s):  
Wei Zhang ◽  
Xiaomin Li ◽  
Wenjuan Zhang ◽  
Yanxia Lu ◽  
Weihao Lin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Target Genes ◽  
Suppressive Effect ◽  
Luciferase Reporter ◽  
Expression Levels ◽  
Non Coding Rna ◽  
Potential Biomarker ◽  
And Migration

BackgroundWe previously reported that the long non-coding RNA (lncRNA) CASC11 promotes colorectal cancer (CRC) progression as an oncogene by binding to HNRNPK. However, it remains unknown whether CASC11 can act as a competitive endogenous RNA (ceRNA) in CRC. In this study, we focused on the role of CASC11 as a ceRNA in CRC by regulating miR-646 and miR-381-3p targeting of RAB11FIP2.MethodsWe identified the target microRNAs (miRNAs) of CASC11 and the target genes of miR-646 and miR-381-3p using bioinformatic methods. A dual-luciferase reporter assay was performed to validate the target relationship. Quantitative real-time PCR (qRT-PCR), western blotting (WB), and immunohistochemistry (IHC) were used to measure the RNA and protein expression levels. Rescue experiments in vitro and in vivo were performed to investigate the influence of the CASC11/miR-646 and miR-381-3p/RAB11FIP2 axis on CRC progression.ResultsWe found that CASC11 binds to miR-646 and miR-381-3p in the cytoplasm of CRC cells. Moreover, miR-646 and miR-381-3p inhibitors reversed the suppressive effect of CASC11 silencing on CRC growth and metastasis in vitro and in vivo. We further confirmed that RAB11FIP2 is a mutual target of miR-646 and miR-381-3p. The expression levels of CASC11 and RAB11FIP2 in CRC were positively correlated and reciprocally regulated. Further study showed that CASC11 played an important role in regulating PI3K/AKT pathway by miR-646 and miR-381-3p/RAB11FIP2 axis.ConclusionOur study showed that CASC11 promotes the progression of CRC as a ceRNA by sponging miR-646 and miR-381-3p. Thus, CASC11 is a potential biomarker and a therapeutic target of CRC.

scholarly journals Genome-wide analysis of long non-coding RNA expression and function in colorectal cancer

Tumor Biology ◽  
2017 ◽  
Vol 39 (5) ◽  
pp. 101042831770365 ◽  
Author(s):  
Fangyuan Jing ◽  
Huicheng Jin ◽  
Yingying Mao ◽  
Yingjun Li ◽  
Ye Ding ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Expression Profile ◽  
Colorectal Carcinogenesis ◽  
Rna Expression ◽  
Rna Transcripts ◽  
Non Coding Rna ◽  
Tumor Tissues ◽  
Non Coding Rnas ◽  
Long Non Coding Rna

Long non-coding RNAs (lncRNAs) are widely transcribed in the genome, but their expression profile and roles in colorectal cancer are not well understood. The aim of this study was to investigate the long non-coding RNA expression profile in colorectal cancer and look for potential diagnostic biomarkers of colorectal cancer. Long non-coding RNA microarray was applied to investigate the global long non-coding RNA expression profile in colorectal cancer. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed using standard enrichment computational methods. The expression levels of selected long non-coding RNAs were validated by quantitative reverse transcription polymerase chain reaction. The relationship between long non-coding RNA expression levels and clinicopathological characteristics of colorectal cancer patients was assessed. Coexpression analyses were carried out to find the coexpressed genes of differentially expressed long non-coding RNAs, followed by gene ontology analysis to predict the possible role of the selected long non-coding RNAs in colorectal carcinogenesis. In this study, a total of 1596 long non-coding RNA transcripts and 1866 messenger RNA transcripts were dysregulated in tumor tissues compared with paired normal tissues. The top upregulated long non-coding RNAs in tumor tissues were CCAT1, UCA1, RP5-881L22.5, NOS2P3, and BC005081 and the top downregulated long non-coding RNAs were AK055386, AC078941.1, RP4-800J21.3, RP11-628E19.3, and RP11-384P7.7. Long non-coding RNA UCA1 was significantly upregulated in colon cancer, and AK055386 was significantly downregulated in tumor with dimension <5 cm. Functional prediction analyses showed that both the long non-coding RNAs coexpress with cell cycle related messenger RNAs. The current long non-coding RNA study provided novel insights into expression profile in colorectal cancer and predicted the potential roles of long non-coding RNAs in colorectal carcinogenesis. Among the dysregulated long non-coding RNAs, UCA1 was found to be associated with anatomic site, and AK055386 was found associated with tumor size. Further functional investigations into the molecular mechanisms are warranted to clarify the role of long non-coding RNA in colorectal carcinogenesis.

scholarly journals Long Non-Coding RNA CBR3-AS1 Promotes Stem-Like Properties and Oxaliplatin Resistance of Colorectal Cancer by Sponging miR-145-5p

2020 ◽  
Author(s):  
Liangbao Xie ◽  
Guangfei Cui ◽  
Tao Li
Keyword(s):  
Colorectal Cancer ◽  
Direct Interaction ◽  
Luciferase Reporter ◽  
Expression Levels ◽  
Mammosphere Formation ◽  
Normal Tissues ◽  
Non Coding Rna ◽  
Rna Immunoprecipitation ◽  
Long Non Coding Rna

Abstract Background: Accumulating evidence has shown that long non-coding RNAs (lncRNAs) serve as essential regulators in a plethora of human cancers. In this study, we analyzed the expression profile and functional role of lncRNA CBR3-AS1 in colorectal cancer (CRC).Methods: CRC tissues and paired adjacent normal tissues were obtained from 133 patients. The expression levels of CBR3-AS1 and miR-145-5p in tissues and cells were detected by RT-qPCR analysis. The proliferation, oxaliplatin resistance, apoptosis, migration, invasion and stem-like properties of CRC cells were detected by MTT assay, flow cytometry analysis, transwell assay and mammosphere formation assay, respectively. Western blot analysis was performed to detect the expression levels of relevant proteins. Dual-luciferase reporter assay and RNA immunoprecipitation assay verified the direct interaction between CBR3-AS1 and miR-145-5p in CRC.Results: High expression levels of CBR3-AS1 were found in CRC tissues and cell lines. Upregulated CBR3-AS1 was closely associated with poor prognosis and adverse clinicopathological features of CRC patients. Artificial knockdown of CBR3-AS1 markedly suppressed the proliferation, migration, invasion and stem-like properties, but promoted the apoptosis of CRC cells. Moreover, we observed that CBR3-AS1 could directly bind to miR-145-5p and negatively regulated its expression in CRC. Further experiments also demonstrated that inhibition of miR-145-5p reverted the effects of CBR3-AS1 knockdown on CRC cells. In addition, compared with the parental cells, CBR3-AS1 expression was strikingly increased in oxaliplatin-resistant CRC cells, and the oxaliplatin resistance was notably diminished by CBR3-AS1 knockdown. Conclusions: To conclude, our study suggested that CBR3-AS1 serves an oncogenic role in CRC, and may be exploited as a novel therapeutic target for CRC patients.

Is There Currently an Established Role for the Use of Predictive or Prognostic Molecular Markers in the Management of Colorectal Cancer? A Point/Counterpoint

2012 ◽  
pp. 193-200
Author(s):  
Alan P. Venook ◽  
Johanna C. Bendell ◽  
Robert S. Warren
Keyword(s):  
Colorectal Cancer ◽  
Colorectal Carcinogenesis ◽  
Myelogenous Leukemia ◽  
Cancer Management ◽  
Positron Emission ◽  
High Incidence ◽  
Breast Cancer Management ◽  
Personalized Oncology ◽  
The Right ◽  
Tract Infections

Overview: The term “personalized oncology” means different things to the oncologist than to the patient. But fundamentally, the phrase creates the expectation that decisions can be informed by the unique features of the patient and patient's cancer. Much like determining antibiotic sensitivities in urinary tract infections, the oncologist is expected to choose the right treatment(s), for each individual patient. Numerous methods can be used to “personalize” management decisions, although truly useful biomarkers continue to escape our grasp. Positron Emission Tomography in patients with GI stromal tumors or genotyping of c-kit in chronic myelogenous leukemia cells can guide the use of imatinib, these scenarios represent a minority of patients. The promise of individualized therapy, however, has led to the commercialization of numerous assays to probe patient's genetic make-up and that of the tumor. Breast cancer management has benefitted from the analysis of gene recurrence scores. More recently the analysis of germline or tumor-associated mutations in non-small cell lung cancer and melanoma has led to clinically meaningful molecular subsets of these diseases, guiding the successful targeting of such cancers with small-molecule inhibitors. Despite the high incidence of colorectal cancer and our relatively long-standing grasp of the molecular pathways in colorectal carcinogenesis, the management of these patients remains mostly empiric and movement toward “personalization” has been slow and incremental. Now, however, molecular imaging and commercial assays for genetic makeup of tumor specimens has put the oncologist and oncologic surgeon in the crossfire with patients and families who believe the era of “personalization” is here.

scholarly journals RIP-Seq of EZH2 Identifies TCONS-00036665 as a Regulator of Myogenesis in Pigs

2021 ◽  
Vol 8 ◽  
Author(s):  
Shanshan Wang ◽  
Xuewen Xu ◽  
Yan Liu ◽  
Jianjun Jin ◽  
Feng Zhu ◽  
...  
Keyword(s):  
Target Gene ◽  
Target Genes ◽  
Bioinformatics Analysis ◽  
Histone H3 ◽  
Mechanistic Studies ◽  
Set Domain ◽  
Polycomb Repressive Complex 2 ◽  
Rna Transcripts ◽  
Non Coding Rna ◽  
Rna Immunoprecipitation

Enhancer of zeste homolog 2 (EZH2) is the catalytic subunit of polycomb repressive complex 2 and contains a SET domain that catalyzes histone H3 trimethylation on lysine 27 (H3K27me3) to generate an epigenetic silencing mark. EZH2 interacts with transcription factors or RNA transcripts to perform its function. In this study, we applied RNA immunoprecipitation sequencing and long intergenic non-coding RNA (lincRNA) sequencing methods to identify EZH2-binding lincRNAs. A total of 356 novel EZH2-binding lincRNAs were identified by bioinformatics analysis and an EZH2-binding lincRNA TCONS-00036665 was characterized. TCONS-00036665 promoted pig skeletal satellite cell proliferation but inhibited cell differentiation, and this function was conserved between pigs and mice. Further mechanistic studies indicated that TCONS-00036665 can bind to EZH2 and recruits EZH2 to the promoters of the target genes p21, MyoG, and Myh4, which leads to the enrichment of H3K27me3 and the repression of target gene expression and pig myogenesis. In conclusion, the lincRNA TCONS-00036665 regulates pig myogenesis through its interaction with EZH2.

A Tale of Two Colons and Two Cancers

Swiss Surgery ◽  
2003 ◽  
Vol 9 (1) ◽  
pp. 3-7 ◽  
Author(s):  
Gervaz ◽  
Bühler ◽  
Scheiwiller ◽  
Morel
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Splenic Flexure ◽  
Chromosomal Instability ◽  
Proximal Colon ◽  
Colorectal Carcinogenesis ◽  
Physiological Data ◽  
Central Hypothesis ◽  
Group Stratification

The central hypothesis explored in this paper is that colorectal cancer (CRC) is a heterogeneous disease. The initial clue to this heterogeneity was provided by genetic findings; however, embryological and physiological data had previously been gathered, showing that proximal (in relation to the splenic flexure) and distal parts of the colon represent distinct entities. Molecular biologists have identified two distinct pathways, microsatellite instability (MSI) and chromosomal instability (CIN), which are involved in CRC progression. In summary, there may be not one, but two colons and two types of colorectal carcinogenesis, with distinct clinical outcome. The implications for the clinicians are two-folds; 1) tumors originating from the proximal colon have a better prognosis due to a high percentage of MSI-positive lesions; and 2) location of the neoplasm in reference to the splenic flexure should be documented before group stratification in future trials of adjuvant chemotherapy in patients with stage II and III colon cancer.

Positron emission tomography in colorectal cancer

2002 ◽  
Vol 13 (2) ◽  
pp. 127-138
Author(s):  
Ronan McDermott ◽  
Farrokh Dehdashti ◽  
Barry A. Siegel
Keyword(s):  
Colorectal Cancer ◽  
Positron Emission Tomography ◽  
Emission Tomography ◽  
Positron Emission
Sign in / Sign up

Export Citation Format

Share Document