Establishment of a Colorectal Cancer-Related MicroRNA-mRNA Regulatory Network by Microarray and Bioinformatics

Abstract

Colorectal cancer (CRC) is one of the most malignant cancers with high morbidity and mortality. MicroRNAs (miRNAs) are small non-coding RNAs that affect biological processes by binding to mRNAs and regulating their expression, and epigenetic alterations including miRNA dysregulation are significantly involved in CRC development. Determining the effect of the miRNA-mRNA network on CRC could be helpful for developing novel therapeutic targets and prognostic biomarkers, and even improving survival. In this study, microarray assays were used to screen differentially expressed miRNAs (DE miRNAs) and mRNAs (DE mRNAs) in CRC and the adjacent normal tissues. Among the detected genes, 42 miRNAs and 142 mRNAs were significantly upregulated in CRC, while 23 miRNAs and 279 mRNAs were significantly downregulated. Through overlapping of predicted targets of DE miRNAs and anti-expressed DE mRNAs, networks of DE miRNAs and DE mRNAs in CRC were established. Additionally, the formation of a protein-protein interaction network of DE mRNAs possibly targeted by DE miRNAs, functional annotation and pathway analysis, stable subnetwork mining, and determination of hub genes provided the probable mechanism used by DE miRNAs and DE mRNAs to regulate CRC growth. Finally, validation of expression and prognostic potential of hub genes provided further support for the results above and indicated that CCL-28, GPR15, PNOC, NUSAP1, and their interacted miRNAs may be a potential signature for prognosis of CRC patients. In sum, we successfully established miRNA-mRNA regulatory networks based on microarray results targeting CRC, and these findings may elucidate the mechanisms used for CRC growth and identify miRNA-related signatures for prognosis and treatment of CRC.

GPR15 in colon cancer development and anti-tumor immune responses

“…The study thus provides a glimpse of possible effects that can be mediated by GPR15 in colon cancer beyond its classical function as a T-cell trafficking protein. Another study on mRNA and miRNA signatures in human COAD patient samples also reported reduced GPR15 expression in tumors and potential miRNA mediated regulation of GPR15 levels in COAD 40 .…”

PNOC Expressed by B Cells in Cholangiocarcinoma Was Survival Related and LAIR2 Could Be a T Cell Exhaustion Biomarker in Tumor Microenvironment: Characterization of Immune Microenvironment Combining Single-Cell and Bulk Sequencing Technology

“…In cancer investigations, PNOC was related to high inflammatory status and oxidative stress in C6 glioma cells, which also was highly up-regulated in pediatric brainstem ganglioglioma tissues and epithelial ovarian cancer, and in analysis of high-risk gastrointestinal stromal tumor, PNOC was reported as a prognostic biomarker ( 45 – 48 ). In a study of mRNA and microRNA network in colorectal cancer, PNOC and its targeting microRNAs were also prognostic markers for evaluation of patients ( 49 ). In our analysis, PNOC was up-regulated in cholangiocarcinoma samples, though the difference didn’t achieve significance.…”

Long-Term Effects of Very Low Dose Particle Radiation on Gene Expression in the Heart: Degenerative Disease Risks

“…First, we used a relaxed cutoff threshold (adjusted p < 0.25), which could include more false positives compared to a stricter cutoff. In contrast, it is well known that a small sample size generally yields higher adjusted p -values [ 83 , 84 , 85 , 86 ]. However, the results of downstream functional analyses and data from previous publications further confirmed the validity of our methodology and findings.…”