Study on miRNAs in Pan-Cancer of the Digestive Tract Based on the Illumina HiSeq System Data Sequencing

Abstract

Objective. miRNA has gained attention as a therapeutic target in various malignancies. The proposal of this study was to investigate the biological functions of key miRNAs and target genes in cancers of the digestive tract which include esophageal carcinoma (ESCA), gastric adenocarcinoma (GAC), colon adenocarcinoma (COAD), and rectal adenocarcinoma (READ). Materials and Methods. After screening differentially expressed miRNAs (DEMIs) and differentially expressed mRNAs (DEMs) in four digestive cancers from The Cancer Genome Atlas (TCGA) database, the diagnostic value of above DEMIs was evaluated by receiver-operating characteristic (ROC) curve analysis. Then, corresponding DEMIs’ target genes were predicted by miRWalk 2.0. Intersection of predicted target genes and DEMs was taken as the target genes of DEMIs, and miRNA-mRNA regulatory networks between DEMIs and target genes were constructed. Meanwhile, the univariate Cox risk regression model was used to screen miRNAs with distinct prognostic value, and Kaplan–Meier analysis was used to determine their significance of prognosis. Furthermore, we performed bioinformatics methods including protein-protein interaction (PPI) networks, gene ontology (GO) annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and gene group RIDA analysis by Gene-Cloud of Biotechnology Information (GCBI) to explore the function and molecular mechanisms of DEMIs and predicted target genes in tumor development. Results. Eventually, 3 DEMIs (miR-7-3, miR-328, and miR-323a) with significant prognostic value were obtained. In addition, 3 DEMIs (miR-490-3p, miR-133a-3p, and miR-552-3p) and 281 target genes were identified, and the 3 DEMIs showed high diagnostic value in READ and moderate diagnostic value in ESCA, GAC, and COAD. Also, the miRNA-mRNA regulatory network with 3 DEMIs and 281 overlapping genes was successfully established. Functional enrichment analysis showed that 281 overlapping genes were mainly related to regulation of cell proliferation, cell migration, and PI3K-Akt signaling pathway. Conclusion. The diagnostic value and prognostic value of significant DEMIs in cancers of the digestive tract were identified, which may provide a novel direction for treatment and prognosis improvement of cancers of the digestive tract.

miR-552: an important post-transcriptional regulator that affects human cancer

“…This result was found in various GC cell lines (AGS, MGC-803, and MKN-45) [29]. In rectal adenocarcinoma (READ), Lai CH et al found that the expression of miR-552 in READ tissues (n=162) was much higher than normal tissues (n=3) in TCGA database [30]. By comparing the expression of miR-552 between 51 osteosarcomas (OS) tissues and 19 adjacent normal tissues, it was found that the expression level of miR-552 was significantly increased in OS tissues [6].…”

“…The expression of miR-552 in HCC is more than twice that of normal tissues [3]. The expression of miR-552 in READ is 3.20 times that of normal tissues [30]. Compared with normal tissues, the expression level of miR-552 in metastatic lung adenocarcinomas is 39 times higher [7].…”

Emerging roles of MiR-133a in human cancers

“…The combination of miR-133a and FOBT could be a potential detection mode in colorectal cancer screening 83 . Based on the information from The Cancer Genome Atlas (TCGA) database and Meta-analysis results, along with bioinformatics analysis, miR-133a was recognized as a potential biomarker of NSCLC 84 - 86 , oral cancer 87 , 88 , osteosarcoma 89 , cervical cancer 90 , prostate cancer 91 , digestive tumors 92 including EC 93 - 95 , GC 96 , 97 , pancreatic ductal adenocarcinoma (PDAC) 98 and CRC 99 . A study of 8006 tumors including 19 tumor types suggested that hypoxia contributed to genomic instability.…”

m5C RNA Methylation Primarily Affects the ErbB and PI3K–Akt Signaling Pathways in Gastrointestinal Cancer

“…At the same time, accumulating evidence has elucidated that the PI3K–Akt signaling pathway is highly activated ( Guo et al, 2015 ; Hao et al, 2019 ) and is a validated therapeutic target in RCC ( Lin et al, 2014 ). Key miRNAs and target genes have been reported to be mainly related to the PI3K–Akt signaling pathway in GI cancers ( Lai et al, 2019 ). A bioinformatics analysis showed that the DEGs of EC compared with normal tissues are mainly enriched in the PI3K–Akt signaling pathway ( Li M. et al, 2020 ; Yu-Jing et al, 2020 ).…”