The regulatory roles of long non-coding RNAs in the development of chemoresistance in breast cancer.

Akshay Malhotra,Aklank Jain,Hridayesh Prakash,Manju Jain,Karen M Vasquez

doi:10.18632/oncotarget.22577

Abstract

Chemoresistance is one of the major hurdles in the treatment of breast cancer, which limits the effect of both targeted and conventional therapies in clinical settings. Therefore, understanding the mechanisms underpinning resistance is paramount for developing strategies to circumvent resistance in breast cancer patients. Several published reports have indicated that lncRNAs play a dynamic role in the regulation of both intrinsic and acquired chemoresistance through a variety of mechanisms that endow cells with a drug-resistant phenotype. Although a number of lncRNAs have been implicated in chemoresistance of breast cancer, their mechanistic roles have not been systematically reviewed. Thus, here we present a detailed review on the latest research findings and discoveries on the mechanisms of acquisition of chemoresistance in breast cancer related to lncRNAs, and how lncRNAs take part in various cancer signalling pathways involved in breast cancer cells. Knowledge obtained from this review could assist in the development of new strategies to avoid or reverse drug resistance in breast cancer chemotherapy.

Highlights

Despite advances in early diagnosis, therapy and surgery, breast cancer is still the leading cause of cancer related death in women worldwide [1, 2]
Such non-coding RNAs are transcribed into a large variety of regulatory RNAs, including piwiinteracting RNAs, microRNAs, small-interfering RNAs, circular RNAs, small Cajal body-specific RNAs, small nucleolar RNAs, transfer RNAs, ribosomal RNAs and long non-coding RNAs [7, 8]
These findings reveal that long non-coding RNAs (lncRNAs) Urothelial carcinoma associated-1 (UCA1) induces chemoresistance to tamoxifen through different molecular pathways, and regulates several other miRNAs involved in breast cancer (Figure 2)

Summary

INTRODUCTION

Despite advances in early diagnosis, therapy and surgery, breast cancer is still the leading cause of cancer related death in women worldwide [1, 2]. The advancement in large-scale whole genome sequencing technologies suggests that less than 2% of the human genome encodes for proteins, whereas much of the remaining genome is transcribed into non-coding RNAs (ncRNAs) [5, 6] Such non-coding RNAs are transcribed into a large variety of regulatory RNAs, including piwiinteracting RNAs (piRNAs), microRNAs (miRNAs), small-interfering RNAs (siRNAs), circular RNAs (circRNAs), small Cajal body-specific RNAs (scaRNAs), small nucleolar RNAs (snoRNAs), transfer RNAs (tRNAs), ribosomal RNAs (rRNAs) and long non-coding RNAs (lncRNAs) [7, 8].

Validation Methods

Findings

CONCLUSIONS