Roles of Long Non-Coding RNAs on Tumorigenesis and Glioma Development

Abstract

More than 98% of eukaryotic tanscriptomes are composed of non-coding RNAs with no functional protein-coding capacity. Those transcripts also include tens of thousands of long non-coding RNAs (lncRNAs) which are emerging as key elements of cellular homeostasis, essentially tumorigenesis steps. However, we are only beginning to understand the nature and extent of the involvement of lncRNAs on tumorigeneis. Here, we highlight recent progresses that have identified a myriad of molecular functions on tumorigenesis for several lncRNAs including metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), prostate cancer associated non-coding RNA 1 (PRNCR1), prostate cancer gene expression marker 1 (PCGEM1), H19, and homeobox transcript antisense intergenic RNA (HOTAIR), and several new lncRNAs for glioma development. Potential therapeutic approaches for the lncRNAs in various human diseases are also discussed.

Keywords: Glioma; Non-coding RNA; Tumorigenesis; lncRNA.

Fig. 1

Schematic diagram of lncRNA action mechanisms. A: Mediators on signaling pathway: lncRNAs can serve as molecular signaling mediators which modulate certain set of gene expression in conjunction with specific transcription factors or chromatin modifiers. B: Molecular decoys: lncRNAs can serve as the molecular decoy which takes away proteins or RNAs from the specific location. C: Work as molecular guides: lncRNAs can serve as the molecular guides by locating certain ribonucleoprotein complexes to specific target site on chromatin. D: Scaffold function: lncRNAs can support the assembly of protein complexes which link the factors together to generate brand new functions. IncRNA: long non-coding RNA.

Fig. 2

Potential therapeutic approaches for targeting lncRNAs. Several methods, including small interfering RNAs (siRNAs), antisense oligonucleotides (ASOs) and ribozymes or deoxyribozymes, can be used to block the function of lncRNAs. A: Synthetic double-stranded short RNA can be delivered to cells and the antisense strand of the siRNA duplex loads on to the RNA-induced silencing complex (RISC) and degrades the targeted lncRNA. B: ASOs are single-stranded, chemically modified DNA oligomers (less than 25 nt in length) that are designed to be complementary to a target lncRNA. ASOs form a heteroduplex with the target lncRNA, and RNase H recognizes the lncRNA-DNA heteroduplex and cleaves the RNA strand. C: However, ribozymes or deoxyribozymes do not dependent on the RISC, which mediates siRNA-induced degradation, or on RNase H. IncRNA: long non-coding RNA.