Small RNAs inhibit bladder cancer by up-regulating tumor suppressor genes

Chenghe Wang ,Zhong Chen ,Zhangqun Ye

doi:10.14800/rd.595

Abstract

RNA activation (RNAa) is a newly discovered mechanism in which non-coding RNAs like small double-stranded RNAs (dsRNAs) or micro RNAs (miRNAs) induce sequence-speciﬁc gene activation by targeting promoter. Although its underlying mechanism remains unclear, we and others have demonstrated that Ago protein, RNA polymerase II (RNA Pol II) and heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2/B1) are required for RNAa. In addition, RNAa is conserved in mammalian cells. Increasing evidences indicated that dsRNAs or miRNAs can induce tumor suppressing genes expression and hold great capacity to inhibit bladder cancer cells. RNAa provides a novel method for gene manipulation and offers an exciting potential for therapeutic modality against bladder cancers. In this review, we will focus on the research advances in exploiting the mechanism of RNAa and its applications in bladder cancer therapeutics.

Highlights

Bladder cancer represents one of the most common malignancy worldwide and has a high mortality [1]
We focus on the observations up to now on small activating RNAs (saRNAs) mediated tumor suppressing genes activation in bladder cancer, especially its applications in cancer therapy and gene functional research in bladder cancer
We have reported that a double-stranded RNAs (dsRNAs) targeting the promoter of p21 at -322 relative to transcriptional start site (TSS) has the capacity to induce p21 expression in human bladder cancer cell lines and significantly inhibits bladder cancer cells proliferation and clonogenicity, causes acceleration of cell apoptosis and accumulation in G0/G1 phase in vitro [28]

Summary

Introduction

Bladder cancer represents one of the most common malignancy worldwide and has a high mortality [1]. Small double-stranded RNAs (dsRNAs) or micro RNAs (miRNAs) have been known to induce gene expression by targeting promoter or antisense of transcripts [5,6,7,8]. This positive gene regulation phenomenon was referred to as RNA activation (RNAa) and the dsRNAs were termed as small activating RNAs (saRNAs).

Results

Conclusion