scholarly journals Exosomal miRNA: Small Molecules, Big Impact in Colorectal Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-18 ◽  
Author(s):  
Valentin Vautrot ◽  
Gaëtan Chanteloup ◽  
Mohammed Elmallah ◽  
Marine Cordonnier ◽  
François Aubin ◽  
...  

Colorectal cancer (CRC) is one of the major causes of cancer-related deaths worldwide. Tumor microenvironment (TME) contains many cell types including stromal cells, immune cells, and endothelial cells. The TME modulation explains the heterogeneity of response to therapy observed in patients. In this context, exosomes are emerging as major contributors in cancer biology. Indeed, exosomes are implicated in tumor proliferation, angiogenesis, invasion, and premetastatic niche formation. They contain bioactive molecules such as proteins, lipids, and RNAs. More recently, many studies on exosomes have focused on miRNAs, small noncoding RNA molecules able to influence protein expression. In this review, we describe miRNAs transported by exosomes in the context of CRC and discuss their influence on TME and their potential as circulating biomarkers. This overview underlines emerging roles for exosomal miRNAs in cancer research for the near future.

mSystems ◽  
2018 ◽  
Vol 3 (3) ◽  
Author(s):  
Ce Yuan ◽  
Michael B. Burns ◽  
Subbaya Subramanian ◽  
Ran Blekhman

ABSTRACT Although variation in gut microbiome composition has been linked with colorectal cancer (CRC), the factors that mediate the interactions between CRC tumors and the microbiome are poorly understood. MicroRNAs (miRNAs) are known to regulate CRC progression and are associated with patient survival outcomes. In addition, recent studies suggested that host miRNAs can also regulate bacterial growth and influence the composition of the gut microbiome. Here, we investigated the association between miRNA expression and microbiome composition in human CRC tumor and normal tissues. We identified 76 miRNAs as differentially expressed (DE) in tissue from CRC tumors and normal tissue, including the known oncogenic miRNAs miR-182, miR-503, and mir-17~92 cluster. These DE miRNAs were correlated with the relative abundances of several bacterial taxa, including Firmicutes , Bacteroidetes , and Proteobacteria . Bacteria correlated with DE miRNAs were enriched with distinct predicted metabolic categories. Additionally, we found that miRNAs that correlated with CRC-associated bacteria are predicted to regulate targets that are relevant for host-microbiome interactions and highlight a possible role for miRNA-driven glycan production in the recruitment of pathogenic microbial taxa. Our work characterized a global relationship between microbial community composition and miRNA expression in human CRC tissues. IMPORTANCE Recent studies have found an association between colorectal cancer (CRC) and the gut microbiota. One potential mechanism by which the microbiota can influence host physiology is through affecting gene expression in host cells. MicroRNAs (miRNAs) are small noncoding RNA molecules that can regulate gene expression and have important roles in cancer development. Here, we investigated the link between the gut microbiota and the expression of miRNA in CRC. We found that dozens of miRNAs are differentially regulated in CRC tumors and adjacent normal colon and that these miRNAs are correlated with the abundance of microbes in the tumor microenvironment. Moreover, we found that microbes that have been previously associated with CRC are correlated with miRNAs that regulate genes related to interactions with microbes. Notably, these miRNAs likely regulate glycan production, which is important for the recruitment of pathogenic microbial taxa to the tumor. This work provides a first systems-level map of the association between microbes and host miRNAs in the context of CRC and provides targets for further experimental validation and potential interventions.


2018 ◽  
Author(s):  
Matlock A Jeffries

Autoimmunity refers to a pathologic state of immunologic dysregulation in which the human immune system turns inward, attacking healthy tissues. The key step in this process is a break of self-immune tolerance. Recent studies have implicated dysregulation of gene expression via altered epigenetic control as a key mechanism in the development and promotion of autoimmunity. Epigenetics is defined as heritable changes in gene expression as a result of modification of DNA methylation, histone side chains, and noncoding RNA. Studies examining identical twins discordant for lupus, for example, were among the first to identify alterations in DNA methylation leading to lupus. Histone side-chain changes have been studied extensively in rheumatoid arthritis (RA), and many pathogenic cell types in RA exhibit a hyperacetylation phenotype. Finally, new research in the noncoding RNA field has not only uncovered potentially targetable pathways (e.g., miR-155) but may lead to the development of new diagnostic and prognostic biomarkers, helping physicians better tailor specific treatment regimens to improve response to therapy in autoimmune disease.   This review contains 4 figures, 1 table and 47 references Key Words: autoimmunity, big data, biomarkers, computational biology, DNA methylation, epigenetics, histone acetylation, histone methylation, microRNA, noncoding RNA


2021 ◽  
Vol 21 ◽  
Author(s):  
Afsane Bahrami ◽  
Gordon A. Ferns

: MicroRNAs (miRs) is a class of conserved, small, noncoding RNA molecules which modulate gene expression post-transcriptionally. miR-148b is a member of miR-148/152 family generally known to be a tumor suppressor via its affect on different signaling pathways and regulatory genes. Aberrant expression of miR-148b has recently been shown to be responsible for tumorigenesis for several different cancer types. This review discusses the current evidences regarding the involvement of miR-148b expression in human cancers and its potential clinical importance for tumor diagnosis, prognosis, and therapeutics.


3 Biotech ◽  
2020 ◽  
Vol 10 (12) ◽  
Author(s):  
Sujay Paul ◽  
Luis M. Ruiz-Manriquez ◽  
Francisco I. Serrano-Cano ◽  
Carolina Estrada-Meza ◽  
Karla A. Solorio-Diaz ◽  
...  

AbstractMicroRNAs (miRNAs) are a group of small noncoding RNA molecules with significant capacity to regulate the gene expression at the post-transcriptional level in a sequence-specific manner either through translation repression or mRNA degradation triggering a fine-tuning biological impact. They have been implicated in several processes, including cell growth and development, signal transduction, cell proliferation and differentiation, metabolism, apoptosis, inflammation, and immune response modulation. However, over the last few years, extensive studies have shown the relevance of miRNAs in human pathophysiology. Common human parasitic diseases, such as Malaria, Leishmaniasis, Amoebiasis, Chagas disease, Schistosomiasis, Toxoplasmosis, Cryptosporidiosis, Clonorchiasis, and Echinococcosis are the leading cause of death worldwide. Thus, identifying and characterizing parasite-specific miRNAs and their host targets, as well as host-related miRNAs, are important for a deeper understanding of the pathophysiology of parasite-specific diseases at the molecular level. In this review, we have demonstrated the impact of human microRNAs during host−parasite interaction as well as their potential to be used for diagnosis and prognosis purposes.


2019 ◽  
Vol 101 (6) ◽  
pp. 1167-1178 ◽  
Author(s):  
Sarah Bjorkman ◽  
Hugh S Taylor

AbstractMicroRNAs (miRNAs), a class of small noncoding RNA molecules, have been recognized as key post-transcriptional regulators associated with a multitude of human diseases. Global expression profiling studies have uncovered hundreds of miRNAs that are dysregulated in several diseases, and yielded many candidate biomarkers. This review will focus on miRNAs in endometriosis, a common chronic disease affecting nearly 10% of reproductive-aged women, which can cause pelvic pain, infertility, and a myriad of other symptoms. Endometriosis has delayed time to diagnosis when compared to other chronic diseases, as there is no current accurate, easily accessible, and noninvasive tool for diagnosis. Specific miRNAs have been identified as potential biomarkers for this disease in multiple studies. These and other miRNAs have been linked to target genes and functional pathways in disease-specific pathophysiology. Highlighting investigations into the roles of tissue and circulating miRNAs in endometriosis, published through June 2018, this review summarizes new connections between miRNA expression and the pathophysiology of endometriosis, including impacts on fertility. Future applications of miRNA biomarkers for precision medicine in diagnosing and managing endometriosis treatment are also discussed.


2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Jian Wang ◽  
Yong Du ◽  
Xiaoming Liu ◽  
William C. Cho ◽  
Yinxue Yang

MicroRNAs (miRNAs) are a class of small, noncoding RNA molecules capable of regulating gene expression translationally and/or transcriptionally. A large number of evidence have demonstrated that miRNAs have a functional role in both physiological and pathological processes by regulating the expression of their target genes. Recently, the functionalities of miRNAs in the initiation, progression, angiogenesis, metastasis, and chemoresistance of tumors have gained increasing attentions. Particularly, the alteration of miRNA profiles has been correlated with the transformation and metastasis of various cancers, including colon cancer. This paper reports the latest findings on miRNAs involved in different signaling networks leading to colon cancer metastasis, mainly focusing on miRNA profiling and their roles in PTEN/PI3K, EGFR, TGFβ, and p53 signaling pathways of metastatic colon cancer. The potential of miRNAs used as biomarkers in the diagnosis, prognosis, and therapeutic targets in colon cancer is also discussed.


2020 ◽  
Vol 27 (2) ◽  
pp. 66-71
Author(s):  
Ozal Arzuman Beylerli ◽  
Ilgiz F. Gareev ◽  
Valentin N. Pavlov

MicroRNAs (miRNAs) are a class of small noncoding RNA molecules that negatively regulate gene expression at posttranscriptional levels. MiRNAs regulate many normal physiological processes, and also play an important role in the development of most disorders. The expression levels of miRNAs are characterized by endogenous properties and tissue specificity. These characteristics increase the likelihood that miRNAs can serve as useful clinical biomarkers in the diagnosis of certain diseases. Chronic lower back pain is usually associated with degeneration of the intervertebral disc (IDD), which is closely associated with apoptosis, impaired extracellular matrix, cell proliferation, and an inflammatory response. This process is characterized by a cascade of molecular, cellular, biochemical, and structural changes. Currently, there is no clinical therapy that shows the pathophysiology of disk degeneration. The presence of unregulated expression of miRNA in patients with degenerative disk disease indicates a vital role of miRNAs in the pathogenesis of IDD. It becomes apparent that epigenetic processes affect the evolution of IDD as much as the genetic background. Deregulated phenotypes of pulp nucleus cells, including differentiation, migration, proliferation, and apoptosis, are involved in all stages of the progression of human IDD. In this review, we will focus on the role and therapeutic value of miRNAs in IDD.


2012 ◽  
Vol 35 (4) ◽  
pp. 285-295 ◽  
Author(s):  
Yimin Zhu ◽  
Xingyuan Xiao ◽  
Lairong Dong ◽  
Zhiming Liu

MicroRNAs are small noncoding RNA molecules that control expression of target genes. Our previous studies show that let-7a decreased in gastric carcinoma and that up-regulation of let-7a by gene augmentation inhibited gastric carcinoma cell growth bothin vitroandin vivo, whereas it remains largely unclear as to how let-7a affects tumor growth. In this study, proteins associated with the function of let-7a were detected by high throughout screening. The cell line of SGC-7901 stablely overexpressing let-7a was successfully established by gene cloning. Two-dimensional gel electrophoresis (2-DEy was used to separate the total proteins of SGC-7901/let-7a, SGC-7901/EV and SGC-7901, and PDQuest software was applied to analyze 2-DE images. Ten different protein spots were identified by MALDI-TOF-MS, and they may be the proteins associated with let-7a function. The overexpressed proteins included Antioxidant protein 2, Insulin–like growth factor binding protein 2, Protein disulfide isomerase A2, C-1-tetrahydrofolate synthase, Cyclin-dependent kinase inhibitor1 (CDKN1) and Rho–GTPase activating protein 4. The underexpressed proteins consisted of S-phase kinase-associated protein 2 (Spk2), Platelet membrane glycoprotein, Fibronectin and Cks1 protein. Furthermore, the different expression levels of the partial proteins (CDKN1, Spk2 and Fibronectin) were confirmed by western blot analysis. The data suggest that these differential proteins are involved in a novel let-7a signal pathway and these findings provide the basis to investigate the functional mechanisms of let-7a in gastric carcinoma.


2021 ◽  
Vol 12 ◽  
Author(s):  
Aysegül Aksan ◽  
Karima Farrag ◽  
Sami Aksan ◽  
Oliver Schroeder ◽  
Jürgen Stein

Iron deficiency, with or without anemia, is the most frequent hematological manifestation in individuals with cancer, and is especially common in patients with colorectal cancer. Iron is a vital micronutrient that plays an essential role in many biological functions, in the context of which it has been found to be intimately linked to cancer biology. To date, however, whereas a large number of studies have comprehensively investigated and reviewed the effects of excess iron on cancer initiation and progression, potential interrelations of iron deficiency with cancer have been largely neglected and are not well-defined. Emerging evidence indicates that reduced iron intake and low systemic iron levels are associated with the pathogenesis of colorectal cancer, suggesting that optimal iron intake must be carefully balanced to avoid both iron deficiency and iron excess. Since iron is vital in the maintenance of immunological functions, insufficient iron availability may enhance oncogenicity by impairing immunosurveillance for neoplastic changes and potentially altering the tumor immune microenvironment. Data from clinical studies support these concepts, showing that iron deficiency is associated with inferior outcomes and reduced response to therapy in patients with colorectal cancer. Here, we elucidate cancer-related effects of iron deficiency, examine preclinical and clinical evidence of its role in tumorigenesis, cancer progression and treatment response. and highlight the importance of adequate iron supplementation to limit these outcomes.


2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 139-139 ◽  
Author(s):  
Sara Moscovita Falzarano ◽  
Ming Zhou ◽  
Paula Carver ◽  
Eric A. Klein ◽  
Robert Dreicer ◽  
...  

139 Background: Taxanes are microtubule-stabilizing drugs used investigationally in adjuvant and neoadjuvant settings of prostate cancer (PCA) treatment in an attempt to improve systemic control of high risk disease. Understanding mechanism of response to taxanes is an essential step in developing novel combination therapies to improve PCA response rates. MicroRNAs (miRNAs) are small noncoding RNA molecules that negatively regulate gene expression by binding target messenger RNAs and inhibiting their stability and/or translation. In cancer miRNAs can act as oncogenes and/or tumor suppressor genes. The objective of our study was to identify miRNAs that are affected by neoadjuvant docetaxel in high-risk PCA. Methods: Whole cell RNA was extracted from formalin-fixed paraffin-embedded (FFPE) radical prostatectomy specimens from 8 patients with high grade PCA treated with neoadjuvant docetaxel, 8 high grade untreated PCA and their corresponding untreated non-neoplastic tissue. Tumors were matched by Gleason score, patient age and year of surgery. The expression of 88 cancer-associated miRNAs was then quantified using a PCR-based miRNA microarray assay. Results: Thirty-eight (43%) of the 88 analyzed miRNAs (including miR-205, miR-222, and miR-1) were sgnificantly downregulated in untreated PCA compared with untreated non-neoplastic tissue, and one (miR-183) was upregulated. Twenty (23%) miRNAs (including miR-218, miR-124, and let-7b) were significantly upregulated in treated compared to untreated PCA. The expression levels of 16 of these miRNAs (including miR-9, miR-133b, and miR-27b) were reverted to values similar to untreated non-neoplastic prostatic tissue, as a result of docetaxel treatment. Conclusions: Our results indicate a potential role of miRNAs in PCA response to taxanes. A subset of miRNAs are downregulated in untreated tumors but upregulated in treated PCA to the levels compared to untreated non-neoplastic tissue, suggesting a miRNA modulation towards a non-neoplastic expression profile with neoadjuvant docetaxel treatment. Further studies are underway to evaluate the miRNA-mediated effects of taxanes in PCA.


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