MicroRNAs associated with metastatic prostate cancer - PubMed (original) (raw)

MicroRNAs associated with metastatic prostate cancer

Akira Watahiki et al. PLoS One. 2011.

Abstract

Objective: Metastasis is the most common cause of death of prostate cancer patients. Identification of specific metastasis biomarkers and novel therapeutic targets is considered essential for improved prognosis and management of the disease. MicroRNAs (miRNAs) form a class of non-coding small RNA molecules considered to be key regulators of gene expression. Their dysregulation has been shown to play a role in cancer onset, progression and metastasis, and miRNAs represent a promising new class of cancer biomarkers. The objective of this study was to identify down- and up-regulated miRNAs in prostate cancer that could provide potential biomarkers and/or therapeutic targets for prostate cancer metastasis.

Methods: Next generation sequencing technology was applied to identify differentially expressed miRNAs in a transplantable metastatic versus a non-metastatic prostate cancer xenograft line, both derived from one patient's primary cancer. The xenografts were developed via subrenal capsule grafting of cancer tissue into NOD/SCID mice, a methodology that tends to preserve properties of the original cancers (e.g., tumor heterogeneity, genetic profiles).

Results: Differentially expressed known miRNAs, isomiRs and 36 novel miRNAs were identified. A number of these miRNAs (21/104) have previously been reported to show similar down- or up-regulation in prostate cancers relative to normal prostate tissue, and some of them (e.g., miR-16, miR-34a, miR-126*, miR-145, miR-205) have been linked to prostate cancer metastasis, supporting the validity of the analytical approach.

Conclusions: The use of metastatic and non-metastatic prostate cancer subrenal capsule xenografts derived from one patient's cancer makes it likely that the differentially expressed miRNAs identified in this study include potential biomarkers and/or therapeutic targets for human prostate cancer metastasis.

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Conflict of interest statement

Competing Interests: The authors declare that no competing interests exist.

Figures

Figure 1

Figure 1. Effects of overexpression of miR-486 on proliferation and tissue invasiveness of 22Rv1 human prostate cancer cells.

A) As indicated by MTT assay, there was no significant difference between the growth of miR-486-transfected cells and control cells over a 72-hr period. B) Tissue invasiveness, as measured by Matrigel invasion, of miR-486 transfected cells and control cells. Data are expressed as percent invasiveness ± S.D. and show increased invasiveness of miR-486-transfected cells (85% ; p = 0.08).

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