scholarly journals Colorectal Cancer: From the Genetic Model to Posttranscriptional Regulation by Noncoding RNAs

2017 ◽  
Vol 2017 ◽  
pp. 1-38 ◽  
Author(s):  
María Antonia Lizarbe ◽  
Jorge Calle-Espinosa ◽  
Eva Fernández-Lizarbe ◽  
Sara Fernández-Lizarbe ◽  
Miguel Ángel Robles ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Posttranscriptional Regulation ◽  
Genetic Model ◽  
Treatment Options ◽  
Noncoding Rnas ◽  
Developed Countries ◽  
Colorectal Carcinogenesis ◽  
Special Focus ◽  
Epigenetic Alterations ◽  
And Function

Colorectal cancer is the third most common form of cancer in developed countries and, despite the improvements achieved in its treatment options, remains as one of the main causes of cancer-related death. In this review, we first focus on colorectal carcinogenesis and on the genetic and epigenetic alterations involved. In addition, noncoding RNAs have been shown to be important regulators of gene expression. We present a general overview of what is known about these molecules and their role and dysregulation in cancer, with a special focus on the biogenesis, characteristics, and function of microRNAs. These molecules are important regulators of carcinogenesis, progression, invasion, angiogenesis, and metastases in cancer, including colorectal cancer. For this reason, miRNAs can be used as potential biomarkers for diagnosis, prognosis, and efficacy of chemotherapeutic treatments, or even as therapeutic agents, or as targets by themselves. Thus, this review highlights the importance of miRNAs in the development, progression, diagnosis, and therapy of colorectal cancer and summarizes current therapeutic approaches for the treatment of colorectal cancer.

scholarly journals The Molecular Basis and Therapeutic Potential of Let-7 MicroRNAs against Colorectal Cancer

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Rei Mizuno ◽  
Kenji Kawada ◽  
Yoshiharu Sakai
Keyword(s):  
Colorectal Cancer ◽  
Molecular Basis ◽  
Posttranscriptional Regulation ◽  
Therapeutic Agent ◽  
Therapeutic Potential ◽  
Noncoding Rnas ◽  
Intestinal Tumorigenesis ◽  
C Elegans ◽  
Microrna Family ◽  
Underlying Mechanisms

Although a number of studies have revealed the underlying mechanisms which regulate the development of colorectal cancer (CRC), we have not completely overcome this disease yet. Accumulating evidence has shown that the posttranscriptional regulation by the noncoding RNAs such as microRNAs plays an important role in the development or progression of CRC. Among a number of microRNAs, the let-7 microRNA family that was first discovered in C. elegans and conserved from worms to humans has been linked with the development of many types of cancers including CRC. The expression level of let-7 microRNAs is temporally low during the normal developmental processes, while elevated in the differentiated tissues. The let-7 microRNAs regulate the cell proliferation, cell cycle, apoptosis, metabolism, and stemness. In CRC, expressions of let-7 microRNAs have been reported to be reduced, and so let-7 microRNAs are considered to be a tumor suppressor. In this review, we discuss the mechanisms regulating the let-7 microRNA expression and the downstream targets of let-7 in the context of intestinal tumorigenesis. The application of let-7 mimics is also highlighted as a novel therapeutic agent.

scholarly journals Different Mechanism Involvement in the Formation of Colorectal Cancer; Mega Review

2021 ◽  
Vol 8 (9) ◽  
pp. 558-573
Author(s):  
Muhammad Ali ◽  
Yang Wang ◽  
Qi Zhang
Keyword(s):  
Colorectal Cancer ◽  
Dietary Habits ◽  
Treatment Options ◽  
Developed Countries ◽  
Term Survival ◽  
Keywords Colorectal Cancer ◽  
Cancer Tumor ◽  
Low Incidence ◽  
New Treatment ◽  
New Treatments

Colorectal cancer was infrequently diagnosed several decades ago. Nowadays, it is the world's fourth most deadly cancer with almost 900,000 deaths annually. Colorectal cancer had a low incidence several decades ago. However, it has become predominant cancer and now accounts for approximately 10% of cancer-related mortality in western countries. The ‘rise’ of colorectal cancer in developed countries can be attributed to the increasingly aging population, unfavorable modern dietary habits and an increase in risk factors such as smoking, low physical exercise and obesity. New treatments for primary and metastatic colorectal cancer have emerged, providing additional options for patients; these treatments include laparoscopic surgery for primary disease, more aggressive resection of metastatic disease (such as liver and pulmonary metastases), radiotherapy for rectal cancer and neoadjuvant and palliative chemotherapies. However, these new treatment options have had a limited impact on cure rates and long-term survival. Keywords: Colorectal cancer, Tumor marker, Hereditary colorectal cancer, Mediterranean diet.

A comprehensive overview of colon cancer- a grim reaper of the 21st century

2020 ◽  
Vol 27 ◽  
Author(s):  
Rajesh Kumar ◽  
Seetha Harilal ◽  
Simone Carradori ◽  
Bijo Mathew
Keyword(s):  
Colorectal Cancer ◽  
Treatment Plan ◽  
Treatment Options ◽  
Developed Countries ◽  
Comprehensive Overview ◽  
Genetic Characteristics ◽  
Bacterial Fermentation ◽  
Screening Programs ◽  
Multiple Treatment ◽  
The Individual

: A few decades ago, the incidence of colorectal cancer (CRC) was low and is now the fourth in the list of deadly cancers producing nearly a million deaths annually. A population that is aging along with risk factors such as smoking, obesity, sedentary lifestyle with little or no physical activity, and non-healthy food habits of developed countries can increase the risk of colorectal cancer. The balance in gut microbiota and the metabolites produced during bacterial fermentation within the host play a significant role in regulating intestinal diseases as well as colorectal cancer development. Recent progress in the understanding of illness resulted in multiple treatment options such as surgery, radiation, and chemotherapy including targeted therapy and multitherapies. The treatment plan for CRC depends on location, stage and grade of the cancer as well as genomic biomarker tests. Despite all the advancements made in the genetic and molecular aspects of the disease, the knowledge seems inadequate as the drug action as well as the wide variation in drug response did not appear strongly correlated with the individual molecular and genetic characteristics which suggests the requirement of comprehensive molecular understanding of this complex heterogeneous disease. Furthermore, multitherapies or a broad spectrum approach which is an amalgamation of the various promising as well as effective therapeutic strategies that can tackle heterogeneity and act on several targets of the disease need to be validated in clinical studies. The latest treatment options have significantly increased the survival up to three years in the case of advanced disease. The fact that colorectal cancer is developed from a polypoid precursor as well as the symptoms of the disease occur at an advanced stage, underline how screening programs can help early detection and decrease mortality as well as morbidity from CRC.

scholarly journals MicroRNAs as novel therapeutic targets to treat kidney injury and fibrosis

2016 ◽  
Vol 310 (10) ◽  
pp. F931-F944 ◽  
Author(s):  
Ivan G. Gomez ◽  
Naoki Nakagawa ◽  
Jeremy S. Duffield
Keyword(s):  
Kidney Disease ◽  
Treatment Options ◽  
Noncoding Rnas ◽  
Kidney Injury ◽  
Transcriptional Regulators ◽  
Small Noncoding Rnas ◽  
Pathological Mechanism ◽  
Kidney Disease Progression ◽  
Fibrotic Diseases ◽  
And Function

MicroRNAs (miRs), a class of small noncoding RNAs that act as post-transcriptional regulators of gene expression, have attracted increasing attention as critical regulators of organogenesis, cancer, and disease. Interest has been spurred by development of a novel class of synthetic RNA oligonucleotides with excellent drug-like properties that hybridize to a specific miR, preventing its action. In kidney disease, a small number of miRs are dysregulated. These overlap with regulated miRs in nephrogenesis and kidney cancers. Several dysregulated miRs have been identified in fibrotic diseases of other organs, representing a “fibrotic signature,” and some of these fibrotic miRs contribute remarkably to the pathogenesis of kidney disease. Chronic kidney disease, affecting ∼10% of the population, leads to kidney failure, with few treatment options. Here, we will explore the pathological mechanism of miR-21, whose pre-eminent role in amplifying kidney disease and fibrosis by suppressing mitochondrial biogenesis and function is established. Evolving roles for miR-214, -199, -200, -155, -29, -223, and -126 in kidney disease will be discussed, and we will demonstrate how studying functions of distinct miRs has led to new mechanistic insights for kidney disease progression. Finally, the utility of anti-miR oligonucleotides as potential novel therapeutics to treat chronic disease will be highlighted.

scholarly journals Biomarkers for Stratification in Colorectal Cancer: MicroRNAs

2019 ◽  
Vol 26 (1) ◽  
pp. 107327481986278 ◽  
Author(s):  
Adewale Oluwaseun Fadaka ◽  
Ashley Pretorius ◽  
Ashwil Klein
Keyword(s):  
Colorectal Cancer ◽  
Early Stage ◽  
Noncoding Rnas ◽  
Colorectal Carcinogenesis ◽  
Specific Expression ◽  
Cancer Pathogenesis ◽  
Previous Decade ◽  
Metastatic Process ◽  
Clinical Tools ◽  
Multistep Model

Colorectal cancer (CRC) is one of the most widely recognized and deadly malignancies worldwide. In spite of the fact that the death rates have declined over the previous decade, particularly because of enhanced screening or potential treatment alternatives, CRC still remains the third leading cause of cancer-related mortality in the world, with an estimated incidence of over 1 million new cases and approximately 600 000 deaths estimated yearly. Unlike prostate and lung cancer, CRC is not easily detectable in its early stage, which may also account for its high mortality rate. MicroRNAs (miRNAs) are a class of noncoding RNAs. The roles of these noncoding RNAs have been implicated in cancer pathogenesis, most especially CRC, due to their ability to posttranscriptionally regulate the expression of oncogenes and tumor suppressor genes. Dysregulated expression of many miRNAs regulates the expression of hundreds of growth regulatory genes and pathways that are important in the multistep model of colorectal carcinogenesis. If CRC is detected early, it is a largely treatable disease. Early diagnosis, including the identification of premalignant adenomas, is regarded a major concept for improving patient survival in CRC treatment. Several lines of research suggest that miRNAs are closely implicated in the metastatic process in CRC and some of these miRNAs could be useful as promising clinical tools for identifying specific stages of CRC due to their differential expression. This review discusses the correlation between CRC staging relative to the specific expression of miRNA for early detection, treatment, and disease management.

scholarly journals MicroRNA biogenesis and variability

2013 ◽  
Vol 4 (4) ◽  
pp. 367-380 ◽  
Author(s):  
Jesús García-López ◽  
Miguel A. Brieño-Enríquez ◽  
Jesús del Mazo
Keyword(s):  
Gene Expression ◽  
Posttranscriptional Regulation ◽  
Regulation Of Gene Expression ◽  
Noncoding Rnas ◽  
High Variability ◽  
Regulate Gene Expression ◽  
Alternative Pathways ◽  
Small Noncoding Rnas ◽  
Fine Regulation ◽  
And Function

AbstractMicroRNAs (miRNAs) are cell-endogenous small noncoding RNAs that, through RNA interference, are involved in the posttranscriptional regulation of mRNAs. The biogenesis and function of miRNAs entail multiple elements with different alternative pathways. These confer a high versatility of regulation and a high variability to generate different miRNAs and hence possess a broad potential to regulate gene expression. Here we review the different mechanisms, both canonical and noncanonical, that generate miRNAs in animals. The ‘miRNome’ panorama enhances our knowledge regarding the fine regulation of gene expression and provides new insights concerning normal, as opposed to pathological, cell differentiation and development.

Colorectal Cancer Epigenetics: Complex Simplicity

2011 ◽  
Vol 29 (10) ◽  
pp. 1382-1391 ◽  
Author(s):  
Manon van Engeland ◽  
Sarah Derks ◽  
Kim M. Smits ◽  
Gerrit A. Meijer ◽  
James G. Herman
Keyword(s):  
Colorectal Cancer ◽  
Regulation Of Gene Expression ◽  
Noncoding Rnas ◽  
Genetic Alterations ◽  
Epigenetic Alterations ◽  
Cancer Epigenetics ◽  
The Past ◽  
Additional Layer ◽  
Multiple Levels ◽  
Nucleosomal Occupancy

Colorectal cancer (CRC) has predominantly been considered a genetic disease, characterized by sequential accumulation of genetic alterations. Growing evidence indicates that epigenetic alterations add an additional layer of complexity to the pathogenesis of CRC, and characterize a subgroup of colorectal cancers with a distinct etiology and prognosis. Epigenetic dysregulation in colorectal cancer is organized at multiple levels, involving DNA methylation, histone modifications, nucleosomal occupancy and remodeling, chromatin looping, and noncoding RNAs. Interactions between these processes and complex associations with genetic alterations have recently been unraveled. It appears that CRC epigenetics will be the paradigm for multistep carcinogenesis, as CRC genetics has been for the past three decades. This review integrates recent data on epigenetic regulation of gene expression in CRC and describes how the understanding of these processes will alter the management of CRC.

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.

Surgery for Lung Cancer and the Consequences for the Swallow

2016 ◽  
Vol 1 (13) ◽  
pp. 162-168
Author(s):  
Pippa Hales ◽  
Corinne Mossey-Gaston
Keyword(s):  
Lung Cancer ◽  
Treatment Options ◽  
Vocal Cord Palsy ◽  
Subsequent Treatment ◽  
Physiological Reserve ◽  
Palliative Phase ◽  
And Function ◽  
The Impact ◽  
Swallow Function

Lung cancer is one of the most commonly diagnosed cancers across Northern America and Europe. Treatment options offered are dependent on the type of cancer, the location of the tumor, the staging, and the overall health of the person. When surgery for lung cancer is offered, difficulty swallowing is a potential complication that can have several influencing factors. Surgical interaction with the recurrent laryngeal nerve (RLN) can lead to unilateral vocal cord palsy, altering swallow function and safety. Understanding whether the RLN has been preserved, damaged, or sacrificed is integral to understanding the effect on the swallow and the subsequent treatment options available. There is also the risk of post-surgical reduction of physiological reserve, which can reduce the strength and function of the swallow in addition to any surgery specific complications. As lung cancer has a limited prognosis, the clinician must also factor in the palliative phase, as this can further increase the burden of an already compromised swallow. By understanding the surgery and the implications this may have for the swallow, there is the potential to reduce the impact of post-surgical complications and so improve quality of life (QOL) for people with lung cancer.

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.

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