Targeting long non-coding RNAs in cancers: progress and prospects

Abstract

Pervasive transcription occurs in the human genome to generate thousands of RNA transcripts, and accumulating evidence suggested that the RNA molecules, without protein coding ability, have important roles in diverse biological functions. Long non-coding RNA (lncRNA), with size larger than 200 nt, is a new class of the non-coding RNA that contributes to cancer development and progression. Roles for several lncRNAs in cancers have been characterized and strategies targeting them have inhibitory effects to malignant cells in vitro and in vivo. These findings point to the potential of lncRNAs as prospective novel therapeutic targets in cancers. Recent advance in biological drugs, led by nucleic acid drugs (i.e. siRNAs, antisense oligonucleotides), suggest directions for the development of cancer therapies targeting lncRNAs. Here, we discuss the characteristics of lncRNAs regarding their synthesis, stability and functional role in cells, and emphasize their unique properties that determine their molecular functions. We then discuss the association of lncRNAs with cancers, and illustrate the anticancer effects induced upon modulating the level and function of lncRNAs. We also revisit established methods for targeting RNA molecules and discuss new agents and strategies to attenuate lncRNAs in cancer.

Keywords: ANRIL; ASO; ATRA; CRC; CREB; Cancer; DM1; DsRNA; EMT; Epigenetics; HCC; HOTAIR; HOX transcript antisense intergenic RNA; HULC; HamRz; IRES; LSCC; LincRNA; LncRNA; Long non-coding RNA; MALAT1; NAT; NSCLC; Nucleic acid drugs; ORF; PCGEM1; PCa; RISC; RNA interference; RNA secondary structure; RNAi; RNAi silencing complex; SELEX; T-UCR; TAR; Therapeutic targets; UTR; all-trans retinoic acid; antisense non-coding RNA in the INK4 locus; antisense oligonucleotide; cAMP-responsive element binding protein; colorectal carcinoma; double-stranded RNA; epithelial–mesenchymal transition; hammerhead ribozyme; hepatocellular carcinoma; highly up-regulated in liver cancer; internal ribosomal entry site; laryngeal squamous cell carcinoma; long intergenic non-coding RNA; long non-coding RNA; metastasis associated lung adenocarcinoma transcript 1; myotonic dystrophy type 1; natural antisense transcript; non-small cell lung carcinoma; open reading frame; prostate cancer; prostate cancer gene expression marker 1; shRNA; siRNA; small hairpin RNA; small interfering RNA; systematic evolution of ligands by exponential enrichment; transactivation response element; transcribed ultraconserved region; untranslated region.