Computational Analysis of miRNA and their Gene Targets Significantly Involved in Colorectal Cancer Progression

Background:Globally, colorectal cancer (CRC) is the third most common cancer in women and the fourth most common cancer in men. Dysregulation of small non-coding miRNAs have been correlated with colon cancer progression. Since there are increasing reports of candidate miRNAs as potential biomarkers for CRC, this makes it important to explore common miRNA biomarkers for colon cancer. As computational prediction of miRNA targets is a critical initial step in identifying miRNA: mRNA target interactions for validation, we aim here to construct a potential miRNA network and its gene targets for colon cancer from previously reported candidate miRNAs, inclusive of 10 up- and 9 down-regulated miRNAs from tissues; and 10 circulatory miRNAs. </P><P> Methods: The gene targets were predicted using DIANA-microT-CDS and TarBaseV7.0 databases. Each miRNA and its targets were analyzed further for colon cancer hotspot genes, whereupon DAVID analysis and mirPath were used for KEGG pathway analysis.Results:We have predicted 874 and 157 gene targets for tissue and serum specific miRNA candidates, respectively. The enrichment of miRNA revealed that particularly hsa-miR-424-5p, hsa-miR-96-5p, hsa-miR-1290, hsa-miR-224, hsa-miR-133a and has-miR-363-3p present possible targets for colon cancer hallmark genes, including BRAF, KRAS, EGFR, APC, amongst others. DAVID analysis of miRNA and associated gene targets revealed the KEGG pathways most related to cancer and colon cancer. Similar results were observed in mirPath analysis. A new insight gained in the colon cancer network pathway was the association of hsa-mir-133a and hsa-mir-96-5p with the PI3K-AKT signaling pathway. In the present study, target prediction shows that while hsa-mir-424-5p has an association with mostly 10 colon cancer hallmark genes, only their associations with MAP2 and CCND1 have been experimentally validated.These miRNAs and their targets require further evaluation for a better understanding of their associations, ultimately with the potential to develop novel therapeutic targets.

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A Potential Role of IL-6/IL-6R in the Development and Management of Colon Cancer

Membranes ◽

10.3390/membranes11050312 ◽

2021 ◽

Vol 11 (5) ◽

pp. 312

Author(s):

Mimmo Turano ◽

Francesca Cammarota ◽

Francesca Duraturo ◽

Paola Izzo ◽

Marina De Rosa

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Cancer Progression ◽

Interleukin 6 ◽

Potential Role ◽

Target Cells ◽

Sporadic Colorectal Cancer ◽

Colon Cancer Progression ◽

Interleukin 6 Receptor

Colorectal cancer (CRC) is the third most frequent cancer worldwide and the second greatest cause of cancer deaths. About 75% of all CRCs are sporadic cancers and arise following somatic mutations, while about 10% are hereditary cancers caused by germline mutations in specific genes. Several factors, such as growth factors, cytokines, and genetic or epigenetic alterations in specific oncogenes or tumor-suppressor genes, play a role during the adenoma–carcinoma sequence. Recent studies have reported an increase in interleukin-6 (IL-6) and soluble interleukin-6 receptor (sIL-6R) levels in the sera of patients affected by colon cancer that correlate with the tumor size, suggesting a potential role for IL-6 in colon cancer progression. IL-6 is a pleiotropic cytokine showing both pro- and anti-inflammatory roles. Two different types of IL-6 signaling are known. Classic IL-6 signaling involves the binding of IL-6 to its membrane receptor on the surfaces of target cells; alternatively, IL-6 binds to sIL-6R in a process called IL-6 trans-signaling. The activation of IL-6 trans-signaling by metalloproteinases has been described during colon cancer progression and metastasis, involving a shift from membrane-bound interleukin-6 receptor (IL-6R) expression on the tumor cell surface toward the release of soluble IL-6R. In this review, we aim to shed light on the role of IL-6 signaling pathway alterations in sporadic colorectal cancer and the development of familial polyposis syndrome. Furthermore, we evaluate the possible roles of IL-6 and IL-6R as biomarkers useful in disease follow-up and as potential targets for therapy, such as monoclonal antibodies against IL-6 or IL-6R, or a food-based approach against IL-6.

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Role of MicroRNAs in Colon Cancer Progression and Metastasis

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530320666200825184924 ◽

2020 ◽

Vol 20 ◽

Author(s):

Shruthi Sanjitha Sampath ◽

Sivaramakrishnan Venkatabalsubramanian ◽

Satish Ramalingam

Keyword(s):

Colon Cancer ◽

Cancer Progression ◽

Target Genes ◽

Tumour Progression ◽

Intestinal Barrier ◽

Colon Cancer Progression ◽

Bowel Diseases ◽

Inflammatory Bowel ◽

Novel Therapeutic Strategies

: MicroRNAs regulate gene expression at the posttranscriptional level by binding to the mRNA of their target genes. The dysfunction of miRNAs is strongly associated with the inflammation of the colon. Besides, some microRNAs are shown to suppress tumours while others promote tumour progression and metastasis. Inflammatory bowel diseases include Crohn’s disease and Ulcerative colitis which increase the risk factor for inflammation-associated colon cancer. MicroRNAs are shown to be involved in gastrointestinal pathologies, by targeting the transcripts encoding proteins of the intestinal barrier and their regulators that are associated with inflammation and colon cancer. Detection of these microRNAs in the blood, serum, tissues, faecal matter, etc will enable us to use these microRNAs as biomarkers for early detection of the associated malignancies and design novel therapeutic strategies to overcome the same. Information on MicroRNAs can be applied for the development of targeted therapies against inflammation-mediated colon cancer.

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Animal Models of Colorectal Cancer: From Spontaneous to Genetically Engineered Models and Their Applications

Veterinary Sciences ◽

10.3390/vetsci8040059 ◽

2021 ◽

Vol 8 (4) ◽

pp. 59

Author(s):

Elisabete Nascimento-Gonçalves ◽

Bruno A.L. Mendes ◽

Rita Silva-Reis ◽

Ana I. Faustino-Rocha ◽

Adelina Gama ◽

...

Keyword(s):

Colorectal Cancer ◽

Animal Models ◽

Cancer Progression ◽

Social Impact ◽

Genetically Engineered ◽

In Vivo Studies ◽

Gastrointestinal Malignancies ◽

Advantages And Disadvantages ◽

Colon Cancer Progression

Colorectal cancer is one of the most common gastrointestinal malignancies in humans, affecting approximately 1.8 million people worldwide. This disease has a major social impact and high treatment costs. Animal models allow us to understand and follow the colon cancer progression; thus, in vivo studies are essential to improve and discover new ways of prevention and treatment. Dietary natural products have been under investigation for better and natural prevention, envisioning to show their potential. This manuscript intends to provide the readers a review of rodent colorectal cancer models available in the literature, highlighting their advantages and disadvantages, as well as their potential in the evaluation of several drugs and natural compounds’ effects on colorectal cancer.

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Proteins are potent biomarkers to detect colon cancer progression

Saudi Journal of Biological Sciences ◽

10.1016/j.sjbs.2014.09.017 ◽

2017 ◽

Vol 24 (6) ◽

pp. 1212-1221 ◽

Cited By ~ 12

Author(s):

Palaniselvam Kuppusamy ◽

Natanamurugaraj Govindan ◽

Mashitah M. Yusoff ◽

Solachuddin J.A. Ichwan

Keyword(s):

Colon Cancer ◽

Cancer Progression ◽

Colon Cancer Progression

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The upregulation of PYCR2 is associated with aggressive colon cancer progression and a poor prognosis

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2021.07.084 ◽

2021 ◽

Vol 572 ◽

pp. 20-26

Author(s):

Sitong Wang ◽

Linaer Gu ◽

Lili Huang ◽

Juemin Fang ◽

Zhuqing Liu ◽

...

Keyword(s):

Colon Cancer ◽

Cancer Progression ◽

Poor Prognosis ◽

Colon Cancer Progression

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Cyst(e)ine in nutrition formulation promotes colon cancer growth and chemoresistance by activating mTORC1 and scavenging ROS

Signal Transduction and Targeted Therapy ◽

10.1038/s41392-021-00581-9 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Jiao Wu ◽

Sai-Ching Jim Yeung ◽

Sicheng Liu ◽

Aiham Qdaisat ◽

Dewei Jiang ◽

...

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Weight Loss ◽

Cancer Patients ◽

Cancer Cell ◽

Cancer Progression ◽

Colorectal Cancer Patient ◽

Nutrition Support ◽

Immunodeficient Mice ◽

The Impact

AbstractWeight loss and cachexia are common problems in colorectal cancer patients; thus, parenteral and enteral nutrition support play important roles in cancer care. However, the impact of nonessential amino acid components of nutritional intake on cancer progression has not been fully studied. In this study, we discovered that gastrointestinal cancer patients who received cysteine as part of the parenteral nutrition had shorter overall survival (P < 0.001) than those who did not. Cystine indeed robustly promotes colon cancer cell growth in vitro and in immunodeficient mice, predominately by inhibiting SESN2 transcription via the GCN2-ATF4 axis, resulting in mTORC1 activation. mTORC1 inhibitors Rapamycin and Everolimus block cystine-induced cancer cell proliferation. In addition, cystine confers resistance to oxaliplatin and irinotecan chemotherapy by quenching chemotherapy-induced reactive oxygen species via synthesizing glutathione. We demonstrated that dietary deprivation of cystine suppressed colon cancer xenograft growth without weight loss in mice and boosted the antitumor effect of oxaliplatin. These findings indicate that cyst(e)ine, as part of supplemental nutrition, plays an important role in colorectal cancer and manipulation of cyst(e)ine content in nutritional formulations may optimize colorectal cancer patient survival.

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