RNA-directed epigenetic silencing of Periostin inhibits cell motility.

Nicholas C Lister,Kevin V Morris,Matthew Clemson

doi:10.1098/rsos.140545

Abstract

The over-expression of Periostin, a member of the fasciclin family of proteins, has been reported in a number of cancers and, in particular, in metastatic tumours. These include breast, ovarian, lung, colon, head and neck, pancreatic, prostate, neuroblastoma and thyroid cancers. It is thought that Periostin plays a major role in the development of metastases owing to its apparent involvement in restructuring of the extracellular matrix to create a microenvironment favouring invasion and metastases, angiogenesis, independent proliferation, avoidance of apoptosis and the ability for cells to re-enter the cell cycle. As such we reasoned that targeted suppression of Periostin at the promoter and epigenetic level could result in the stable inhibition of cell motility. We find here that promoter-directed small antisense non-coding RNAs can induce transcriptional gene silencing of Periostin that results ultimately in a loss of cellular motility. The observations presented here suggest that cell motility and possibly metastasis can be controlled by transcriptional and epigenetic regulation of Periostin, offering a potentially new and novel manner to control the spread of cancerous cells.

Highlights

Periostin is an approximately 90 kDa matricellular protein capable of altering interactions between the extracellular matrix and surrounding cells [1,2]
Its structure contains a fourfold repeating domain that shows sequence homology with fasciclin 1, a protein found in insects, which interacts with integrins at the plasma membrane to accommodate motility and cell adhesion [1,3,4]
We report here on a small antisense non-coding RNAs (sasRNAs) that can direct transcriptional gene silencing (TGS) of Periostin resulting in the inhibition of cell metastasis

Summary

Introduction

Periostin is an approximately 90 kDa matricellular protein capable of altering interactions between the extracellular matrix and surrounding cells [1,2]. One pathway for inducing stable long-term transcriptional gene silencing (TGS) involves targeting a genes promoter with small antisense non-coding RNAs (sasRNAs; reviewed in [13]) (figure 1a). As such we hypothesized that sasRNAs targeted to direct TGS of Periostin could inhibit invasive and metastatic potential of cancer cells.

Results

Conclusion