Identification and analysis of the molecular targets of statins in colorectal cancer.

Colorectal cancer (CRC) is the third most common cancer in the world. According to several types of research, statins may impact the development and treatment of CRC. This work aimed to use bioinformatics to discover the relationship between statin targets and differentially expressed genes (DEGs) in CRC patients and determine the possible molecular effect of statins on CRC suppression. We used CRC datasets from the GEO database to select CRC-related DEGs. DGIdb and STITCH databases were used to identify gene targets of subtypes of statin. Further, we identified the statin target of CRC DEGs hub genes by using a Venn diagram of CRC DEGs and statin targets. Funrich and enrichr databases were carried out for the KEGG pathway and gene ontology (GO) enrichment analysis, respectively. GSE74604 and GSE10950 were used to identify CRC DEGs. After analyzing datasets,1370 genes were identified as CRC DEGs, and 345 targets were found for statins. We found that 35 genes are CRC DEGs statin targets. We found that statin targets in CRC were enriched in the receptor and metallopeptidase activity for molecular function, cytoplasm and plasma membrane for cellular component, signal transduction, and cell communication for biological process genes were substantially enriched based on FunRich enrichment. Analysis of the KEGG pathways revealed that the overexpressed DEGs were enriched in the IL-17, PPAR, and Toll-like receptor signaling pathways. Finally, CCNB1, DNMT1, AURKB, RAC1, PPARGC1A, CDKN1A, CAV1, IL1B, and HSPD1 were identified as hub CRC DEGs statin targets. The genetic and molecular aspects of our findings reveal that statins might have a therapeutic effect on CRC.

Impact of curcumin on ferroptosis-related genes in colorectal cancer: Insights from in-silico and in-vitro studies.

Colorectal cancer (CRC) is responsible for a significant number of cancer-related fatalities worldwide. Researchers are investigating the therapeutic potential of ferroptosis, a type of iron-dependent controlled cell death, in the context of CRC. Curcumin, a natural compound found in turmeric, exhibits anticancer properties. This study explores the effects of curcumin on genes related to ferroptosis (FRGs) in CRC. To gather CRC data, we used the Gene Expression Profiling Interactive Analysis (GEPIA) and Gene Expression Omnibus (GEO) databases, while FRGs were obtained from the FerrDb database and PubMed. We identified 739 CRC differentially expressed genes (DEGs) in CRC and discovered 39 genes that were common genes between FRGs and CRC DEGs. The DEGs related to ferroptosis were enriched with various biological processes and molecular functions, including the regulation of signal transduction and glucose metabolism. Using the Drug Gene Interaction Database (DGIdb), we predicted drugs targeting CRC-DEGs and identified 17 potential drug targets. Additionally, we identified eight essential proteins related to ferroptosis in CRC, including MYC, IL1B, and SLC1A5. Survival analysis revealed that alterations in gene expression of CDC25A, DDR2, FABP4, IL1B, SNCA, and TFAM were associated with prognosis in CRC patients. In SW480 human CRC cells, treatment with curcumin decreased the expression of MYC, IL1B, and EZH2 mRNA, while simultaneously increasing the expression of SLCA5 and CAV1. The findings of this study suggest that curcumin could regulate FRGs in CRC and have the potential to be utilized as a therapeutic agent for treating CRC.

Deciphering colorectal cancer progression features and prognostic signature by single-cell RNA sequencing pseudotime trajectory analysis.

Colorectal cancer is the third most common cancer and second cancer with the highest mortality rate in the world. Progression, which leads to metastasis, is one of the biggest challenges in cancer treatment, and despite improvement in screening and treatment techniques, 5 years of survival of colorectal cancer patients drop from 91% in stage I to 12% in stage IV. Single-cell RNA sequencing is one of the most powerful tools to study complex diseases such as cancer, and despite its recent emergence, it's rapidly growing. In contrast to bulk RNA sequencing, which averages out expression of thousands of cells, single-cell RNA sequencing can capture intra-tumor heterogeneity. Moreover, cellular dynamic events like progression can be studied by pseudotime trajectory analysis of single-cell RNA sequencing data. Herein we used Samsung Medical Center (SMC) colorectal cancer single-cell RNA sequencing dataset to find important tumor epithelial cells subtypes. Subsequently, we've found important genes with a dynamic pattern along cancer progression by using pseudo-time trajectory analysis. Also, we found TGFB1 and IL1B as effective ligands and several transcription factors which may regulate the expression of pseudo-time related genes. In the end, we've constructed a LASSO cox regression using 20 psudotime genes, which can predict 3-year survival of colorectal cancer patients with AUC >0.7.

Inducing apoptosis by using microRNA in radio-resistant prostate cancer: an in-silico study with an in-vitro validation.

BACKGROUND: One of the problems with radiation therapy (RT) is that prostate tumor cells are often radio-resistant, which results in treatment failure. This study aimed to determine the procedure involved in radio-resistant prostate cancer apoptosis. For a deeper insight, we devoted a novel bioinformatics approach to analyze the targeting between microRNAs and radio-resistant prostate cancer genes. METHOD: This study uses the Tarbase, and the Mirtarbase databases as validated experimental databases and mirDIP as a predicted database to identify microRNAs that target radio-resistant anti-apoptotic genes. These genes are used to construct the radio-resistant prostate cancer genes network using the online tool STRING. The validation of causing apoptosis by using microRNA was confirmed with flow cytometry of Annexin V. RESULTS: The anti-apoptotic gene of radio-resistant prostate cancer included BCL-2, MCL1, XIAP, STAT3, NOTCH1, REL, REL B, BIRC3, and AKT1 genes. These genes were identified as anti-apoptotic genes for radio-resistant prostate cancer. The crucial microRNA that knockdown all of these genes was hsa-miR-7-5p. The highest rate of apoptotic cells in a cell transfected with hsa-miR-7-5p was (32.90 ± 1.49), plenti III (21.99 ± 3.72), and the control group (5.08 ± 0.88) in 0 Gy (P < 0.001); also, this rate was in miR-7-5p (47.01 ± 2.48), plenti III (33.79 ± 3.40), and the control group (16.98 ± 3.11) (P < 0.001) for 4 Gy. CONCLUSION: The use of this new treatment such as gene therapy to suppress genes involved in apoptosis can help to improve the treatment results and increase the quality of life of patients with prostate cancer.

Screening and introduction of key cell cycle microRNAs deregulated in colorectal cancer by integrated bioinformatics analysis.

Colorectal cancer (CRC) is the second most common cancer in women and the third most common in men worldwide. Impaired cell cycle regulation leads to many cancers and is also approved in CRC. Therefore, cell cycle regulation is a critical therapeutic target for CRC. Furthermore, miRNAs have been discovered as regulators in a variety of cancer-related pathways. This study is designed to investigate how miRNAs and mRNAs interact to regulate the cell cycle in CRC patients. Utilizing the Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Expression Omnibus (GEO), and Therapeutic Target Database (TTD), cell cycle-associated genes were identified and evaluated. Seven of the 22 differentially expressed genes (DEGs) implicated in the cell cycle in three GSEs (GSE24514, GSE10950, and GSE74604) were identified as potential therapeutic targets. Then, using PyRx software, we performed docking proteins with selected drugs. The results demonstrated that these drugs are appropriate molecules for targeting cell cycle DEGs. Tarbase, miRTarbase, miRDIP, and miRCancer databases were used to find miRNAs that target the indicated genes. The ability of these six miRNAs to impact the cell cycle in colorectal cancer may be concluded. These miRNAs were found to be downregulated in SW480 cells when compared to the normal tissue. Our data imply that a precise selection of bioinformatics tools can facilitate the identification of miRNAs that impact mRNA translation at different stages of the cell cycle. The candidates can be investigated more as targets for cell cycle arrest in cancers.

Effect of diabetes on efferocytosis process.

Diabetes is a complex of genetic, metabolic, and autoimmune disorders that are characterized by hyperglycemia. Elevated apoptotic cell count following defective clearance of dead cells that can cause chronic inflammation is a hallmark of the diabetic wound. Effective dead cell clearance is a prerequisite for rapid inflammation resolution and successful recovery. Efferocytosis is a multistep process in which phagocytes engulf the dead cells. Cell body elimination is of great significance in disease and homeostasis. Recent research has clarified that diabetic wounds have an enhanced load of the apoptotic cell, which is partly attributed to the dysfunction of macrophages in apoptotic clearance at the site of the diabetic wounds. In the current work, we highlight the pathways implicated in efferocytosis, from the diagnosis of apoptotic cells to the phagocytic swallowing and the homeostatic resolution, and explain the possible pathophysiological episodes occurring when the proceeding is abrogated. Also, we describe the last development in the management of inflammation in diabetes wound and future directions of surveillance.