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An integrative network biology analysis identifies miR-508-3p as the determinant and a prognosis biomarker of the mesenchymal subtype ovarian cancer

ABSTRACT: An integrative network biology analysis identifies miR-508-3p as the determinant and a prognosis biomarker of the mesenchymal subtype ovarian cancer

PROVIDER: PRJNA428968 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6449840.fastq.gz	Fastqsanger.gz
	SRR6449841.fastq.gz	Fastqsanger.gz
	SRR6449834.fastq.gz	Fastqsanger.gz
	SRR6449835.fastq.gz	Fastqsanger.gz
	SRR6449836.fastq.gz	Fastqsanger.gz

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An integrative network biology analysis identifies miR-508-3p as the determinant and a prognosis biomarker of the mesenchymal subtype ovarian cancer

Project description:Recently, several research groups have identified the mesenchymal subtype of serous OvCa on the basis of transcriptome data and its potential correlation with poor prognosis. We set out to define the regulatory mechanisms underlying the distinct gene expression profiles of serous OvCa using a network-based approach involving multiple molecular modalities such as gene expression and microRNA (miR) expression. Our study demonstrated that the mir-508-3p presented as the most powerful determinant of mesenchymal subtype-specific gene expression, tuning the majority of genes differentially expressed in the poor prognosis subtype, including genes associated with the epithelial–mesenchymal transition (EMT) program. Consequent functional experiments illustrate that miR-508-3p inhibition promoted EMT process, in vitro cell migration and invasion, and in vivo cancer metastasis.

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Integrative network biology analysis identifies miR-508-3p as the determinant for the mesenchymal identity and a strong prognostic biomarker of ovarian cancer.

Project description:Ovarian cancer is a heterogeneous malignancy that poses tremendous clinical challenge. Based on unsupervised classification of whole-genome gene expression profiles, four molecular subtypes of ovarian cancer were recently identified. However, single-driver molecular events specific to these subtypes have not been clearly elucidated. We aim to characterize the regulatory mechanisms underlying the poor prognosis mesenchymal subtype of ovarian cancer using a systems biology approach, involving a variety of molecular modalities including gene and microRNA expression profiles. miR-508-3p emerged as the most powerful determinant that regulates a cascade of dysregulated genes in the mesenchymal subtype, including core genes involved in epithelial-mesenchymal transition (EMT) program. Moreover, miR-508-3p down-regulation, due to promoter hypermethylation, was directly correlated with metastatic behaviors in vitro and in vivo. Taken together, our multidimensional network analysis identified miR-508-3p as a master regulator that defines the mesenchymal subtype and provides a novel prognostic biomarker to improve management of this disease.

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