Closing Editorial: Colorectal Cancer-A Molecular Genetics Perspective.

Colorectal cancer (CRC) remains a significant global health challenge, ranking third in incidence and second in mortality among all cancers [...

From Crypts to Cancer: A Holistic Perspective on Colorectal Carcinogenesis and Therapeutic Strategies.

Colorectal cancer (CRC) represents a significant global health burden, with high incidence and mortality rates worldwide. Recent progress in research highlights the distinct clinical and molecular characteristics of colon versus rectal cancers, underscoring tumor location's importance in treatment approaches. This article provides a comprehensive review of our current understanding of CRC epidemiology, risk factors, molecular pathogenesis, and management strategies.

IL-2RG as a possible immunotherapeutic target in CRC predicting poor prognosis and regulated by miR-7-5p and miR-26b-5p.

Despite advances in treatment strategies, colorectal cancer (CRC) continues to cause significant morbidity and mortality, with mounting evidence a close link between immune system dysfunctions issued. Interleukin-2 receptor gamma (IL-2RG) plays a pivotal role as a common subunit receptor in the IL-2 family cytokines and activates the JAK-STAT pathway. This study delves into the role of Interleukin-2 receptor gamma (IL-2RG) within the tumor microenvironment and investigates potential microRNAs (miRNAs) that directly inhibit IL-2RG, aiming to discern their impact on CRC clinical outcomes.

Platelet-derived microparticles provoke chronic lymphocytic leukemia malignancy through metabolic reprogramming.

Background: It is well established that inflammation and platelets promote multiple processes of cancer malignancy. Recently, platelets have received attention for their role in carcinogenesis through the production of microvesicles or platelet-derived microparticles (PMPs), which transfer their biological content to cancer cells. We have previously characterized a new subpopulation of these microparticles (termed mito-microparticles), which package functional mitochondria.

Circular RNA Expression Signatures Provide Promising Diagnostic and Therapeutic Biomarkers for Chronic Lymphocytic Leukemia.

Chronic lymphocytic leukemia (CLL) is a known hematologic malignancy associated with a growing incidence and post-treatment relapse. Hence, finding a reliable diagnostic biomarker for CLL is crucial. Circular RNAs (circRNAs) represent a new class of RNA involved in many biological processes and diseases.

Characterization of exogenous αSN response genes and their relation to Parkinson's disease using network analyses.

Despite extensive research, the molecular mechanisms underlying the toxicity of αSN in Parkinson's disease (PD) pathology are still poorly understood. To address this, we used a microarray dataset to identify genes that are induced and differentially expressed after exposure to toxic αSN aggregates, which we call (EASR) genes. Using systems biology approaches, we then determined, at multiple levels of analysis, how these EASR genes could be related to PD pathology.

The Pleiotropy of Gene Products and Function.

PAX5, a member of the Paired Box (PAX) transcription factor family, is an essential factor for B-lineage identity during lymphoid differentiation. Mechanistically, PAX5 controls gene expression profiles, which are pivotal to cellular processes such as viability, proliferation, and differentiation. Given its crucial function in B-cell development, aberrant expression also correlates with hallmark cancer processes leading to hematological and other types of cancer lesions.

Pax-5 Protein Expression Is Regulated by Transcriptional 3'UTR Editing.

The gene encodes a transcription factor that is essential for B-cell commitment and maturation. However, deregulation is associated with various cancer lesions, notably hematopoietic cancers. Mechanistically, studies have characterized genetic alterations within the -5 locus that result in either dominant oncogenic function or haploinsufficiency-inducing mutations leading to oncogenesis.

Can hypoxia-inducible factor-1α overexpression discriminate human colorectal cancers with different microsatellite instability?

Clinicopathological features of high-frequency microsatellite instability (MSI-H) colorectal cancers (CRCs) are different from low-frequency MSI (MSI-L) and microsatellite stable (MSS) CRCs. The clinical features of MSI-L cases are unknown, and although the tumors usually show instability for dinucleotide markers, evaluation based on dinucleotides alone could lead to the misclassification of MSI-L or MSS as MSI-H. In this research, we investigated the usefulness of hypoxia-inducible factor-1α (HIF-1α) expression to discriminate MSI-L from MSS and MSI-H in human CRC.

Identification of a stool long non-coding RNAs panel as a potential biomarker for early detection of colorectal cancer.

Background: The feces of colorectal cancer (CRC) patients contain tumor colonocytes, which constantly shed into the lumen area. Therefore, stool evaluation can be considered as a rapid and low-risk way to directly determine the colon and rectum status. As long non-coding RNAs (lncRNAs) alterations are important in cancer cells fate regulation, we aimed to assess the level of a panel of cancer-related lncRNAs in fecal colonocytes.

Establishment of a CALU, AURKA, and MCM2 gene panel for discrimination of metastasis from primary colon and lung cancers.

Metastasis is known as a key step in cancer recurrence and could be stimulated by multiple factors. Calumenin (CALU) is one of these factors which has a direct impact on cancer metastasis and yet, its underlined mechanisms have not been completely elucidated. The current study was aimed to identify CALU co-expressed genes, their signaling pathways, and expression status within the human cancers.

Development and validation of a lipogenic genes panel for diagnosis and recurrence of colorectal cancer.

Background & Aim: Accumulated evidence indicates that the elevation of lipid metabolism is an essential step in colorectal cancer (CRC) development, and analysis of the key lipogenic mediators may lead to identifying the new clinically useful prognostic gene signatures.

Methods: The expression pattern of 61 lipogenic genes was assessed between CRC tumors and matched adjacent normal tissues in a training set (n = 257) with the Mann-Whitney U test. Cox's proportional hazards model and the Kaplan-Meier method were used to identifying a lipogenic-biomarkers signature associated with the prognosis of CRC.

miR-497-5p mediates starvation-induced death in colon cancer cells by targeting acyl-CoA synthetase-5 and modulation of lipid metabolism.

Modulation of fatty acids metabolism is an appropriate strategy for starvation-induced death in tumor cancers. Colon cancer cells express a high level of acyl-CoA synthetase-5 (ACSL5), and as yet no therapeutic approach has been achieved. Herein, ACSL5-related microRNAs (miRNAs) were identified via TargetScan, and their impacts on ACSL5 and lipid content along with metabolic activity, cell cycle, migration, and invasion of colorectal cancer (CRC) cells were examined, and subsequently compared with transcriptome for better visualization of intracellular-signaling networks.

miR-298 plays a pivotal role in colon cancer invasiveness by targeting PTEN.

Evidence indicate that the miR-298 dysregulation might associate with colorectal cancer (CRC) development. Herein, we evaluated the effect of miR-298 dysregulation on colon cancer invasiveness. First, metabolic activity, cell cycle progression, apoptosis, and invasion of miR-298 overexpressed/knocked out colon cancer cells were examined and combined with their transcriptome analysis data for better visualization of miR-298 intracellular signaling networks.

Study of the Antidiabetic Activity of Fruits Aqueous Extract on the Alloxan-Diabetic Wistar Rats.

Pancreatic β-cells dysfunction and impairment of insulin action usually leads to hyperglycemia. is a well-known traditional herbal remedy in Iran due to its positive effects on ameliorating blood glucose homeostasis. In this study, Alloxan-diabetic male Wistar rats were administrated with pomegranate fruits aqueous extract (PE) in different doses of 100, 200, and 350 mg/kg bw (PE+Da, PE+Db and PE+Dc, respectively), and the effects of PE polyphenols content on glucose metabolism in treated groups were examined using oral glucose tolerance test (OGTT), short-term and long-term PE consumption periods models followed by evaluation of plasma insulin, free fatty acids, and triglycerides levels and tissues contents of glycogen and triglycerides; compared with diabetic control (DC) and healthy control (NC) groups.

Investigating the diagnostic performance of HOTTIP, PVT1, and UCA1 long noncoding RNAs as a predictive panel for the screening of colorectal cancer patients with lymph node metastasis.

Like other noncoding RNAs (ncRNAs), dysregulation of long ncRNAs (lncRNAs) has been associated with various clinicopathological features of colorectal cancer (CRC) patients such as lymph node metastasis (LNM). Recently, three aberrant expressed oncogenic lncRNA (onco-lncRNAs), including HOXA transcript at the distal tip (HOTTIP), plasmacytoma variant translocation 1 (PVT1), and urothelial carcinoma associated 1 (UCA1) have been reported in LNM. Herein, we compared the diagnostic performance of these lncRNAs as individual biomarkers and as a discriminating panel between LNM CRC patients, nonmetastatic lymph nodes (NLN) and normal healthy subjects.

A detailed image of rutin underlying intracellular signaling pathways in human SW480 colorectal cancer cells based on miRNAs-lncRNAs-mRNAs-TFs interactions.

Natural dietary ingredients like flavonoids are important for body improvement against diseases. The flavonol rutin is widely found in fruits and vegetables and shows significant anticancer properties. However, the underlined signaling pathways have not been elucidated yet.

HER2 mCRC patients with exon 20 R784G substitution mutation do not respond to the cetuximab therapy.

The human epidermal growth factor 2 (HER2) gene undergoes various mutations that could alter its activity or respond to the antibody therapies. Cetuximab, a known anti-EGFR monoclonal antibody (mAB), is widely administered in metastatic colorectal cancer (mCRC) cases. Here we identified mCRC patients who did not respond to cetuximab (500 mg/m , q2w) after fluoropyrimidine/oxaliplatin regimen failure.

Intratumoral infiltrating lymphocytes correlate with improved survival in colorectal cancer patients: Independent of oncogenetic features.

Background: The clinical relevance and prognostic value of tumor-infiltrating lymphocytes (TILs) as an interplay between malignant cells and immune function has been known for decades. On contrary, this potential may be different by T lymphocytes subsets endowed with a different function. Colorectal cancer (CRC) is a heterogeneous disease with different suggested prognostic biomarkers.

The Application of Gene Expression Profiling in Predictions of Occult Lymph Node Metastasis in Colorectal Cancer Patients.

A key factor in determining the likely outcome for a patient with colorectal cancer is whether or not the tumour has metastasised to the lymph nodes-information which is also important in assessing any possibilities of lymph node resection so as to improve survival. In this review we perform a wide-range assessment of literature relating to recent developments in gene expression profiling (GEP) of the primary tumour, to determine their utility in assessing node status. A set of characteristic genes seems to be involved in the prediction of lymph node metastasis (LNM) in colorectal patients.

Punica granatum L. Fruit Aqueous Extract Suppresses Reactive Oxygen Species-Mediated p53/p65/miR-145 Expressions followed by Elevated Levels of irs-1 in Alloxan-Diabetic Rats.

Objectives: Reactive oxygen species (ROS) is an apoptosis inducer in pancreatic β-cells that stimulates p53/p65 mediated microRNA (miR)-145 expression. Punica granatum L. (pomegranate) is an antioxidant fruit that attenuates ROS generation.

Coexistence of and Mutations in Colorectal Cancer: A Case Report Supporting The Concept of Tumoral Heterogeneity.

The detection of and mutations is a crucial step for the correct therapeutic approach and predicting the epidermal growth factor receptor (EGFR)-targeted therapy resistance of colorectal carcinomas. The concomitant and mutations occur rarely in the colorectal cancers (CRCs) with the prevalence of less than 0.001% of the cases.

Dopaminergic Induction of Umbilical Cord Mesenchymal Stem Cells by Conditioned Medium of Choroid Plexus Epithelial Cells Reduces Apomorphine-Induced Rotation in Parkinsonian Rats.

Background/objective: Degeneration of dopaminergic neurons in Parkinson's disease (PD) implies cell replacement using potentially differentiable sources as a promising therapeutic solution. We tested the capacity of conditioned medium from choroid plexus epithelial cells (CPECs-CM) to induce the dopaminergic potential of umbilical cord matrix mesenchymal stem cells (UCMSCs).

Methods: We isolated UCMSCs from human umbilical cord and CPECs from rat brain.

Shikonin protects dopaminergic cell line PC12 against 6-hydroxydopamine-mediated neurotoxicity via both glutathione-dependent and independent pathways and by inhibiting apoptosis.

We have investigated the mechanism of shikonin function on protection of dopaminergic neurons against 6-OHDA-induced neurotoxicity. Treatment of rat pheochromocytoma cell line PC12 by serial dilutions of shikonin determined 10 μM of the compound as its optimum concentration for protection saving nearly 70 % of the cells against toxicity. Reverse transcription-PCR analysis of shikonin-treated cells showed threefold increase in mRNA levels of glutathione peroxidase-1 (GPX-1) as a representative component of the intracellular anti-oxidant defense system.

Upregulation of glutathione peroxidase-1 expression and activity by glial cell line-derived neurotrophic factor promotes high-level protection of PC12 cells against 6-hydroxydopamine and hydrogen peroxide toxicities.

We examined the impact of strong co-presence and function of glutathione peroxidase-1 (GPX-1) and glial cell line-derived neurotrophic factor (GDNF) on protecting the rat dopaminergic pheochromocytoma cell line PC12 against 6-hydroxydopamine (6-OHDA) and hydrogen peroxide (H₂O₂) toxicities. Primarily, GPX-1 over-expression by PC12 cells infected with pLV-GPX1 lentivirus vectors significantly increased cell survival against 6-OHDA toxicity (p<0.01).