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Novel miRNA-mRNA interactions conserved in essential cancer pathways

View Article: PubMed Central - PubMed

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.

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Related in: MedlinePlus

Genes and miRNAs deregulated almost all of the studied tumour types: SPC24 is differentially overexpressed in all tumour types; SYNE1 is repressed in all tumour types; miR-4746-5p up-regulated in all the tumour types; and miR-145-5p, down-regulated in all tumour types except Cholangiocarcinoma (CHOL).
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f3: Genes and miRNAs deregulated almost all of the studied tumour types: SPC24 is differentially overexpressed in all tumour types; SYNE1 is repressed in all tumour types; miR-4746-5p up-regulated in all the tumour types; and miR-145-5p, down-regulated in all tumour types except Cholangiocarcinoma (CHOL).

Mentions: From the total of 147 significantly deregulated genes (see Supplementary Table 6), we identified SCP24 as the only gene over-expressed in all tumour types. We also found SYNE1 (relevant to the cell cycle) to be the most strongly downregulated gene in the 15 tumours studied (see Fig. 3 for the distribution of both SPC24 and SYNE1). From the remaining differentially expressed genes, 11 belonged to the apoptosis pathway, in which E2F1 and CLSPN were deregulated in 14 and 12 tumour types, respectively. In other pathways, 126 genes appeared to be misregulated in cell cycle pathways and 21 were altered in the DDR, where the oncogenes CDT1, PLK1 and DTL were among the most prominent deregulated genes. In the DNA replication pathway, 26 genes were de-regulated including the previously identified E2F1, CDT1 and the oncogene GINS2 as the most significantly affected genes. Of the 29 genes for senescence that were deregulated, Ubhc10/UBE2C was the most strongly deregulated. Finally, the polymerases DNA2 and POLE2 appeared to be deregulated in the telomere pathway in a large number of tumours.


Novel miRNA-mRNA interactions conserved in essential cancer pathways
Genes and miRNAs deregulated almost all of the studied tumour types: SPC24 is differentially overexpressed in all tumour types; SYNE1 is repressed in all tumour types; miR-4746-5p up-regulated in all the tumour types; and miR-145-5p, down-regulated in all tumour types except Cholangiocarcinoma (CHOL).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5384238&req=5

f3: Genes and miRNAs deregulated almost all of the studied tumour types: SPC24 is differentially overexpressed in all tumour types; SYNE1 is repressed in all tumour types; miR-4746-5p up-regulated in all the tumour types; and miR-145-5p, down-regulated in all tumour types except Cholangiocarcinoma (CHOL).
Mentions: From the total of 147 significantly deregulated genes (see Supplementary Table 6), we identified SCP24 as the only gene over-expressed in all tumour types. We also found SYNE1 (relevant to the cell cycle) to be the most strongly downregulated gene in the 15 tumours studied (see Fig. 3 for the distribution of both SPC24 and SYNE1). From the remaining differentially expressed genes, 11 belonged to the apoptosis pathway, in which E2F1 and CLSPN were deregulated in 14 and 12 tumour types, respectively. In other pathways, 126 genes appeared to be misregulated in cell cycle pathways and 21 were altered in the DDR, where the oncogenes CDT1, PLK1 and DTL were among the most prominent deregulated genes. In the DNA replication pathway, 26 genes were de-regulated including the previously identified E2F1, CDT1 and the oncogene GINS2 as the most significantly affected genes. Of the 29 genes for senescence that were deregulated, Ubhc10/UBE2C was the most strongly deregulated. Finally, the polymerases DNA2 and POLE2 appeared to be deregulated in the telomere pathway in a large number of tumours.

View Article: PubMed Central - PubMed

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.

No MeSH data available.


Related in: MedlinePlus