Novel miRNA-mRNA interactions conserved in essential cancer pathways

Abstract

Cancer is a complex disease in which unrestrained cell proliferation results in tumour development. Extensive research into the molecular mechanisms underlying tumorigenesis has led to the characterization of oncogenes and tumour suppressors that are key elements in cancer growth and progression, as well as that of other important elements like microRNAs. These genes and miRNAs appear to be constitutively deregulated in cancer. To identify signatures of miRNA-mRNA interactions potentially conserved in essential cancer pathways, we have conducted an integrative analysis of transcriptomic data, also taking into account methylation and copy number alterations. We analysed 18,605 raw transcriptome samples from The Cancer Genome Atlas covering 15 of the most common types of human tumours. From this global transcriptome study, we recovered known cancer-associated miRNA-targets and importantly, we identified new potential targets from miRNA families, also analysing the phenotypic outcomes of these genes/mRNAs in terms of survival. Further analyses could lead to novel approaches in cancer therapy.

miR‐24‐3p promotes cell migration and proliferation in lung cancer by targeting SOX7

“…miRNAs regulate many cellular processes such as differentiation, proliferation, migration, and apoptosis . Recent studies have indicated that miRNAs function as oncomiRs or suppressor miRNAs by downregulating cancer suppressor genes or oncogenes . miR‐24‐3p, which belongs to the miR‐24 family, plays a significant role in cancer initiation and progression.…”

Reversal of doxorubicin resistance in lung cancer cells by neferine is explained by nuclear factor erythroid-derived 2-like 2 mediated lung resistance protein down regulation

“…Andrés-León et al [12] analyzed miRNAs in The Cancer Genome Atlas (TCGA) data for HCC and other tumor types. In 2018, a study integrated miRNA expression database (TCGA, GSE31384 [13] , and GSE6857 [14] ) and compared their expression in liver cancer and adjacent normal samples to investigate the difference of miRNAs expression associated with carcinogenesis [15] .…”

CHAPTER 14. Strategies for Safe and Targeted Delivery of MicroRNA Therapeutics

“…In a recent study, the transcriptome of 15 of the most common tumor subtypes was analyzed. 80 the study identified differential expression of 147 genes and 95 miRNAs that were shared in most tumor types. Importantly, 36 paired interactions between the miRNA and the reported targeted transcript were deregulated together.…”

“…this result indicates that a single dysregulated miRNA can alter the expression of its target genes, and that these altered mRNA-miRNA interactions are conserved in cancer pathways between various tumors. 80 therefore, balancing the levels of miRNAs that are dysregulated in cancer, through miRNA-based therapeutic approaches, can potentially impact multiple major signaling pathways in carcinogenesis.…”