scholarly journals A New Light on Potential Therapeutic Targets for Colorectal Cancer Treatment

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1438
Author(s):  
Wei-Lun Tsai ◽  
Chih-Yang Wang ◽  
Yu-Cheng Lee ◽  
Wan-Chun Tang ◽  
Gangga Anuraga ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Biology ◽  
Molecular Mechanisms ◽  
Tumor Development ◽  
Gene Expression Omnibus ◽  
Different Types ◽  
Geo Dataset ◽  
Non Coding Rnas ◽  
Poor Outcomes ◽  
Upregulated Genes

The development and progression of colorectal cancer (CRC) involve changes in genetic and epigenetic levels of oncogenes and/or tumor suppressors. In spite of advances in understanding of the molecular mechanisms involved in CRC, the overall survival rate of CRC still remains relatively low. Thus, more research is needed to discover and investigate effective biomarkers and targets for diagnosing and treating CRC. The roles of long non-coding RNAs (lncRNAs) participating in various aspects of cell biology have been investigated and potentially contribute to tumor development. Our recent study also showed that CRNDE was among the top 20 upregulated genes in CRC clinical tissues compared to normal colorectal tissues by analyzing a Gene Expression Omnibus (GEO) dataset (GSE21815). Although CRNDE is widely reported to be associated with different types of cancer, most studies of CRNDE were limited to examining regulation of its transcription levels, and in-depth mechanistic research is lacking. In the present study, CRNDE was found to be significantly upregulated in CRC patients at an advanced TNM stage, and its high expression was correlated with poor outcomes of CRC patients. In addition, we found that knocking down CRNDE could reduce lipid accumulation through the miR-29b-3p/ANGPTL4 axis and consequently induce autophagy of CRC cells.

LncRNAs: Potential Novel Prognostic and Diagnostic Biomarkers in Colorectal Cancer

2020 ◽  
Vol 27 (30) ◽  
pp. 5067-5077 ◽  
Author(s):  
Narges Dastmalchi ◽  
Reza Safaralizadeh ◽  
Mirsaed Miri Nargesi
Keyword(s):  
Colorectal Cancer ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Ectopic Expression ◽  
Tumor Development ◽  
Diagnostic Biomarkers ◽  
Non Coding Rnas ◽  
Cellular Pathways ◽  
Regulatory Rnas

Background: Long non-coding RNAs (lncRNAs), a type of regulatory RNAs, play a key role in numerous cellular pathways. Ectopic expression of this group of non-coding RNAs has been specified to be involved in numerous diseases. Moreover, the role of lncRNAs in the initiation and development of cancers including colorectal cancer (CRC) has been acknowledged. Objective: In the present review, the role of lncRNAs as prognostic and diagnostic biomarkers in CRC as well as the molecular mechanisms of their contribution to development of CRC has been addressed. Results: The presented studies have indicated the ectopic expression of various lncRNAs in CRC. Some lncRNAs which were considered as tumor suppressors were downregulated in the colorectal cancerous tissues compared with healthy controls; however, some with oncogenic effects were upregulated. LncRNAs contribute to tumor development via various molecular mechanisms such as epigenetically controlling the expression of target genes, interacting with miRNAs as their sponge, etc. Conclusion: LncRNAs that have been recognized as prognostic biomarkers may pave the way for clinical management to offer adjuvant treatments for patients with CRC.

scholarly journals The effective function of circular RNA in colorectal cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Mandana Ameli-Mojarad ◽  
Melika Ameli-Mojarad ◽  
Mahrooyeh Hadizadeh ◽  
Chris Young ◽  
Hosna Babini ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Circular Rna ◽  
Circular Rnas ◽  
Colorectal Tumorigenesis ◽  
Non Coding Rnas ◽  
Mirna Sponges ◽  
Mechanisms Of Development

AbstractColorectal cancer (CRC) is the 3rd most common type of cancer worldwide. Late detection plays role in one-third of annual mortality due to CRC. Therefore, it is essential to find a precise and optimal diagnostic and prognostic biomarker for the identification and treatment of colorectal tumorigenesis. Covalently closed, circular RNAs (circRNAs) are a class of non-coding RNAs, which can have the same function as microRNA (miRNA) sponges, as regulators of splicing and transcription, and as interactors with RNA-binding proteins (RBPs). Therefore, circRNAs have been investigated as specific targets for diagnostic and prognostic detection of CRC. These non-coding RNAs are also linked to metastasis, proliferation, differentiation, migration, angiogenesis, apoptosis, and drug resistance, illustrating the importance of understanding their involvement in the molecular mechanisms of development and progression of CRC. In this review, we present a detailed summary of recent findings relating to the dysregulation of circRNAs and their potential role in CRC.

scholarly journals First person – Elin Schoultz and Ellen Johansson

2021 ◽  
Vol 15 (2) ◽  
Keyword(s):  
Thyroid Gland ◽  
Cell Biology ◽  
Molecular Mechanisms ◽  
Tumor Development ◽  
Neck Region ◽  
Early Career ◽  
Field Cancerization ◽  
First Person ◽  
Head And Neck Region ◽  
Selection Of

ABSTRACT First Person is a series of interviews with the first authors of a selection of papers published in Disease Models & Mechanisms, helping early-career researchers promote themselves alongside their papers. Elin Schoultz and Ellen Johansson are co-first authors on ‘ Tissue architecture delineates field cancerization in BrafV600E-induced tumor development’, published in DMM. Elin is an MD, PhD student in the lab of Mikael Nilsson at Sahlgrenska Centre for Cancer Research, Gothenburg University, Gothenburg. She has a great interest in the thyroid gland in particular, and the mechanisms of tumor development, progression and treatment associated with epithelial carcinomas in general. Ellen is an MD, resident physician in oto-rhino-laryngology and postdoctoral researcher in the lab of Karin Roberg at Department of Biomedical and Clinical Sciences, Division of Cell Biology, Linköping University, Linköping, with broad interest the thyroid gland, tumors of the head and neck region, and the molecular mechanisms that are important for tumor initiation, development, and treatment.

scholarly journals Hepatic Thermal Injury Promotes Colorectal Cancer Engraftment in C57/black 6 Mice

2020 ◽  
Author(s):  
Alison L. Halpern ◽  
J. Gregory Fitz ◽  
Yuki Fujiwara ◽  
Jeniann Yi ◽  
Aimee L. Anderson ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Thermal Ablation ◽  
Thermal Injury ◽  
Tumor Development ◽  
Hepatic Metastases ◽  
Local Environment ◽  
Surgical Approaches ◽  
Recurrence Rates ◽  
Poor Outcomes ◽  
Argon Beam Coagulation

Background:Treatment of liver metastases (primarily colorectal cancer) is limited by high recurrence rates and tumor progression. Surgical approaches to management of these metastases typically utilize heat energy: including electrocautery; argon beam coagulation; thermal ablation of surgical margins for hemostasis; and preemptive thermal ablation to prevent bleeding or effect tumor destruction. Based on high rates of local recurrence, these studies assess whether local effects of hepatic thermal injury (HTI) might contribute to poor outcomes by promoting a hepatic microenvironment favorable for tumor engraftment or progression due to induction of pro-cancer cytokines and deleterious immune infiltrates at the site of thermal injury. Approach and Results:To test this hypothesis, an immunocompetent mouse model was developed wherein HTI was combined with concomitant intrasplenic injection of cells from a well characterized MC38 colon carcinoma cell line. In this model, HTI resulted in a significant increase in engraftment and progression of MC38 tumors at the site of thermal injury. Further, there were local increases in expression of mRNA for Hif1a, Arg1, and Vegfaand activation changes in recruited macrophages at the HTI site but not in untreated liver tissue. Inhibition of HIF1α following HTI significantly reduced discreet hepatic tumor development (p=0.03). Conclusions:Taken together, these findings demonstrate that HTI creates a favorable local environment that is associated with pro-tumorigenic activation of macrophages and circulating tumors implanting. Discrete targeting of HIF1α and/or its up and downstream pathways and/or inhibiting macrophages offer potential strategies for improving the outcome of surgical management of hepatic metastases where HTI is utilized.

scholarly journals The Impact of Diet on the Involvement of Non-Coding RNAs, Extracellular Vesicles, and Gut Microbiome-Virome in Colorectal Cancer Initiation and Progression

2020 ◽  
Vol 10 ◽  
Author(s):  
Bene A. Ekine-Afolabi ◽  
Anoka A. Njan ◽  
Solomon O. Rotimi ◽  
Anu R. I. ◽  
Attia M. Elbehi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Dna Methyltransferase ◽  
Molecular Mechanisms ◽  
Cell Communication ◽  
Extracellular Vesicle ◽  
Dietary Factors ◽  
Tumor Onset ◽  
Non Coding Rnas ◽  
The Impact

Cancer is the major cause of morbidity and mortality in the world today. The third most common cancer and which is most diet related is colorectal cancer (CRC). Although there is complexity and limited understanding in the link between diet and CRC, the advancement in research methods have demonstrated the involvement of non-coding RNAs (ncRNAs) as key regulators of gene expression. MicroRNAs (miRNAs) which are a class of ncRNAs are key players in cancer related pathways in the context of dietary modulation. The involvement of ncRNA in cancer progression has recently been clarified throughout the last decade. ncRNAs are involved in biological processes relating to tumor onset and progression. The advances in research have given insights into cell to cell communication, by highlighting the pivotal involvement of extracellular vesicle (EV) associated-ncRNAs in tumorigenesis. The abundance and stability of EV associated ncRNAs act as a new diagnostic and therapeutic target for cancer. The understanding of the deranging of these molecules in cancer can give access to modulating the expression of the ncRNAs, thereby influencing the cancer phenotype. Food derived exosomes/vesicles (FDE) are gaining interest in the implication of exosomes in cell-cell communication with little or no understanding to date on the role FDE plays. There are resident microbiota in the colon; to which the imbalance in the normal intestinal occurrence leads to chronic inflammation and the production of carcinogenic metabolites that lead to neoplasm. Limited studies have shown the implication of various types of microbiome in CRC incidence, without particular emphasis on fungi and protozoa. This review discusses important dietary factors in relation to the expression of EV-associated ncRNAs in CRC, the impact of diet on the colon ecosystem with particular emphasis on molecular mechanisms of interactions in the ecosystem, the influence of homeostasis regulators such as glutathione, and its conjugating enzyme-glutathione S-transferase (GST) polymorphism on intestinal ecosystem, oxidative stress response, and its relationship to DNA adduct fighting enzyme-0-6-methylguanine-DNA methyltransferase. The understanding of the molecular mechanisms and interaction in the intestinal ecosystem will inform on the diagnostic, preventive and prognosis as well as treatment of CRC.

scholarly journals Relevance of Regulatory T Cells during Colorectal Cancer Development

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1888 ◽  
Author(s):  
Jonadab E. Olguín ◽  
Itzel Medina-Andrade ◽  
Tonathiu Rodríguez ◽  
Miriam Rodríguez-Sosa ◽  
Luis I. Terrazas
Keyword(s):  
Colorectal Cancer ◽  
Immune Response ◽  
T Cells ◽  
Regulatory T Cells ◽  
Tumor Development ◽  
Treg Cells ◽  
Different Types ◽  
Inflammatory Profile ◽  
The Many ◽  
Effector Immune Response

In recent years, there has been a significant increase in the study of own and foreign human factors favoring the development of different types of cancer, including genetic and environmental ones. However, the fact that the immune response plays a fundamental role in the development of immunity and susceptibility to colorectal cancer (CRC) is much stronger. Among the many cell populations of the immune system that participate in restricting or favoring CRC development, regulatory T cells (Treg) play a major role in orchestrating immunomodulation during CRC. In this review, we established concrete evidence supporting the fact that Treg cells have an important role in the promotion of tumor development during CRC, mediating an increasing suppressive capacity which controls the effector immune response, and generating protection for tumors. Furthermore, Treg cells go through a process called “phenotypic plasticity”, where they co-express transcription factors that promote an inflammatory profile. We reunited evidence that describes the interaction between the different effector populations of the immune response and its modulation by Treg cells adapted to the tumor microenvironment, including the mechanisms used by Treg cells to suppress the protective immune response, as well as the different subpopulations of Treg cells participating in tumor progression, generating susceptibility during CRC development. Finally, we discussed whether Treg cells might or might not be a therapeutic target for an effective reduction in the morbidity and mortality caused by CRC.

scholarly journals Identification and integrated analysis of neuropathic pain-related circular RNA signature

2020 ◽  
Author(s):  
Kun Wang ◽  
Zhimin Zhou ◽  
Junping Bao ◽  
Dong Liu ◽  
Yuanbin Hu ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Molecular Mechanisms ◽  
Circular Rna ◽  
Gene Expression Omnibus ◽  
Circular Rnas ◽  
Integrated Analysis ◽  
Biological Processes ◽  
Non Coding Rnas ◽  
Microarray Datasets ◽  
Competitive Endogenous Rna

Abstract Background: More and more evidences show that non-coding RNAs are involved in neuropathic pain, however, there are few reports on the regulatory mechanism of competitive endogenous RNA (ceRNA) in neuropathic pain. The purpose of this study is to explore the possible molecular mechanisms of neuropathic pain. Methods: We collected neuropathic pain-related microarray datasets providing expression profile of circular RNAs (circRNAs) and mRNAs from the Gene Expression Omnibus (GEO) and then performed bioinformatics analysis on them. Results: The present study has identified that up-regulated circRNAs primarily regulate the activity of focal adhesion-associated biological processes and down-regulated primarily regulate the activity of metabolic-associated biological processes by means of ceRNAs. Conclusions: Our data suggest that circRNAs may be candidates for pathogenesis in neuropathic pain and may be considered as promising therapeutic targets in the future.

scholarly journals Genetics of Colorectal Cancer: Role of p53

2020 ◽  
Vol 10 (6-s) ◽  
pp. 183-185
Author(s):  
Rajashri Champanery ◽  
Drashti Joshi
Keyword(s):  
Colorectal Cancer ◽  
Tumor Suppressor ◽  
Tp53 Mutation ◽  
Human Cancer ◽  
Tumor Development ◽  
Tp53 Gene ◽  
Pathological Process ◽  
Functional Roles ◽  
Different Types

The tumor suppressor TP53 gene is one of the most frequently mutated in different types of human cancer. Particularly in colorectal cancer (CRC), it is believed that TP53 mutations play a role in the adenoma-carcinoma transition of tumors during pathological process. The TP53 mutation is the key step driving the transition from adenoma to adenocarcinoma. The functional roles of TP53 mutation in tumor development have been comprehensively investigated. In this mini review, we comprehensively summarize the p53 mutants in CRC progression and discuss the current strategies for p53 mutants in malignancies. Keywords: p53 mutants, colorectal cancer, Tp53 mutation

scholarly journals Integrated aqueous humor ceRNA and miRNA-TF-mRNA network analysis reveals potential molecular mechanisms governing primary open-angle glaucoma pathogenesis

2020 ◽  
Author(s):  
Xiaoqin Wang ◽  
Ming Chen ◽  
Liuzhi Zeng ◽  
Longqian Liu
Keyword(s):  
Gene Expression ◽  
Aqueous Humor ◽  
Molecular Mechanisms ◽  
Primary Open Angle Glaucoma ◽  
Open Angle Glaucoma ◽  
Gene Expression Omnibus ◽  
Open Angle ◽  
Pathway Enrichment ◽  
Protein Protein Interaction ◽  
Non Coding Rnas

AbstractPrimary open-angle glaucoma (POAG) is the leading cause of blindness globally, which develops through complex and poorly understood biological mechanisms. Herein, we conducted an integrated bioinformatics analysis of extant aqueous humor (AH) gene expression datasets in order to identify key genes and regulatory mechanisms governing POAG progression. We downloaded AH gene expression datasets (GSE101727 and GSE105269) corresponding to healthy controls and POAG patients from the Gene Expression Omnibus. We then identified mRNAs, microRNAs (miRNAs), and long non-coding RNAs (lncRNAs) that were differentially expressed (DE) between control and POAG patients. DEmRNAs and DElncRNAs were then subjected to pathway enrichment analyses, after which a protein-protein interaction (PPI) network was generated. This network was then expanded to establish lncRNA-miRNA-mRNA and miRNA-transcription factor(TF)-mRNA networks. In total, the GSE101727 dataset was used to identify 2746 DElncRNAs and 2208 DEmRNAs, while the GSE105269 dataset was used to identify 45 DEmiRNAs. We ultimately constructed a competing endogenous RNA (ceRNA) network incorporating 37, 5, and 14 of these lncRNAs, miRNAs and mRNAs, respectively. The proteins encoded by these 14 hub mRNAs were found to be significantly enriched for activities that may be linked to POAG pathogenesis. In addition, we generated a miRNA-TF-mRNA regulatory network containing 2 miRNAs (miR-135a-5p and miR-139-5p), 5 TFs (TGIF2, TBX5, HNF1A, TCF3, and FOS) and 5 mRNAs (SHISA7, ST6GAC2, TXNIP, FOS, and DCBLD2). The SHISA7, ST6GAC2, TXNIP, FOS, and DCBLD2 genes that may be viable therapeutic targets for the prevention or treatment of POAG, and regulated by the TFs (TGIF2, HNF1A, TCF3, and FOS).

Hypoxia Facilitates the Proliferation of Colorectal Cancer Cells by Inducing Cancer-associated Fibroblast-derived IL6.

2021 ◽  
Author(s):  
Ying Xu ◽  
Rong Kuai ◽  
Yimin Chu ◽  
Lu Zhou ◽  
Hai-qin Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Molecular Mechanisms ◽  
Tumor Development ◽  
Cancer Associated Fibroblast ◽  
Stat3 Signaling ◽  
Colorectal Cancer Cells ◽  
Cancer Tissues ◽  
Development Methods ◽  
Multiplex Cytokine ◽  
Common Malignancy

Abstract Background: Colorectal cancer (CRC) is most common malignancy worldwide, and its underlying molecular mechanisms remain largely unexplored. Accumulating evidences indicate Cancer-Associated Fibroblasts (CAFs), abundant stromal cell population in the tumor microenvironment, play a key role in tumor development. Methods: We have successfully isolated CAFs and paired normal fibroblasts (NFs) from colorectal cancer tissues (n=10). By using multiplex cytokine profiling assay, we have identified IL-6 as a major cytokine released by CAFs. Coculturing of CAFs with CRC cell lines HCT116 or SW480 increase IL-6 release, and the secretion by CAFs can be further enhanced under hypoxia. By using CCK-8 assay, we have found HCT116 or SW480 cells treated with culture medium from CAFs, IL-6 or hypoxia showed a significant cell growth compared to control cells (P<0.01). Results: Mechanistically, we have found hypoxia can enhanced effect of IL-6/STAT3 signaling on CRC cells, in part, throughHIF-1a targets PKM2. Conclusions: In conclusion, our data clearly proposes the interconnected mechanisms for a constitutive activation of STAT3 signalby CAFs-derived IL-6 under hypoxia in colorectal cancer. The pharmacological inhibition of STAT3, PKM2 or HIF-1α can significantly reduce oncogenic effect of IL-6, providing a potential therapeutic target for CRC patients.Trail registration: Not applicable

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