Abstract
Background Accumulating evidences demonstrated that microRNA-target gene pairs were closely related to tumorigenesis and development. However, the correlation between miRNA and target gene was insufficiently understood, especially its changes between tumor and normal tissues. Objectives The aim of this study was to evaluate the changes of correlation of miRNAs-target pairs between normal and tumor. Materials and Methods 5680 mRNA and 5740 miRNA expression profiles of 11 major human cancers were downloaded from the Cancer Genome Atlas (TCGA). The 11 cancer types were bladder urothelial carcinoma, breast invasive carcinoma, head and neck squamous cell carcinoma, kidney chromophobe, kidney renal clear cell carcinoma, kidney renal papillary cell carcinoma, liver hepatocellular carcinoma, lung adenocarcinoma, lung squamous cell carcinoma, stomach adenocarcinoma, and thyroid carcinoma. For each cancer type, we firstly obtained differentially expressed miRNAs (DEMs) and genes (DEGs) in tumor and then acquired critical miRNA-target gene pairs by combining DEMs, DEGs and two experimentally validated miRNA-target interaction databases, miRTarBase and miRecords. We collected samples with both miRNA and mRNA expression values and performed a correlation analysis by Pearson method for miRNA-target pairs in normal and tumor, respectively. Results We totally got 4743 critical miRNA-target pairs across 11 cancer types, and 4572 of them showed weaker correlation in tumor than in normal. The average correlation coefficients of miRNA-target pairs were different greatly between normal (-0.38 ~ -0.61) and tumor (-0.04 ~ -0.26) for 11 cancer type. The pan-cancer network, which consisted of 108 edges connecting 35 miRNAs and 89 target genes, showed the interactions of pairs appeared in multicancers. Conclusions This comprehensive analysis revealed that correlation between miRNAs and target genes was greatly reduced in tumor and these critical pairs we got were involved in cellular adhesion, proliferation, and migration. Our research could provide opportunities for investigating cancer molecular regulatory mechanism and seeking therapeutic targets.
Highlights
Cancer ranks among the most frequent causes of human death worldwide, and its incidence and mortality have risen rapidly recent years [1]
Recent studies have demonstrated that miRNAs play an essential role in carcinogenesis, including cell migration and reproduction, by base pairing with target mRNAs of protein-coding genes [8]
We totally identified 62 ∼ 176 Differentially expressed miRNA DEG (DEM) and 1 483 ∼ 4 875 DEGs for the 11 cancer types (Figure 2)
Summary
Cancer ranks among the most frequent causes of human death worldwide, and its incidence and mortality have risen rapidly recent years [1]. MicroRNAs (miRNAs) are defined as small regulatory RNA molecules with 19-24 nucleotides in length [6] They repress gene expression by binding to complementary sequences in the 3’ untranslated region (3’ UTR) of mRNAs to target them for degradation and thereby prevent their translation [7]. We collected samples with both miRNA and mRNA expression values and performed a correlation analysis by Pearson method for miRNA-target pairs in normal and tumor, respectively. We totally got 4743 critical miRNA-target pairs across 11 cancer types, and 4572 of them showed weaker correlation in tumor than in normal. This comprehensive analysis revealed that correlation between miRNAs and target genes was greatly reduced in tumor and these critical pairs we got were involved in cellular adhesion, proliferation, and migration. Our research could provide opportunities for investigating cancer molecular regulatory mechanism and seeking therapeutic targets
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