LncRNAs: From Basic Research to Medical Application

Abstract

This review aimed to summarize the current research contents about long noncoding RNAs (lncRNAs) and some related lncRNAs as molecular biomarkers or therapy strategies in human cancer and cardiovascular diseases. Following the development of various kinds of sequencing technologies, lncRNAs have become one of the most unknown areas that need to be explored. First, the definition and classification of lncRNAs were constantly amended and supplemented because of their complexity and diversity. Second, several methods and strategies have been developed to study the characteristic of lncRNAs, including new species identifications, subcellular localization, gain or loss of function, molecular interaction, and bioinformatics analysis. Third, based on the present results from basic researches, the working mechanisms of lncRNAs were proved to be different forms of interactions involving DNAs, RNAs, and proteins. Fourth, lncRNA can play different important roles during the embryogenesis and organ differentiations. Finally, because of the tissue-specific expression of lncRNAs, they could be used as biomarkers or therapy targets and effectively applied in different kinds of diseases, such as human cancer and cardiovascular diseases.

Keywords: cancer; cardiovascular diseases; lncRNA; molecular biomarker; therapy strategy.

Figure 1

The classification of lncRNAs: (A) divergent (pancRNA: They originate from the opposite strand of the same promoter region of protein coding gene as the adjacent) and convergent (They encoded on the opposite strands and facing each other); (B) intronic (They transcribed from an intron of another gene); (C) intergenic (They located distant from other genes, usually >10kb); (D) overlapping sense (They overlapped with other genes on the same strand) and overlapping antisense (They overlapped with other genes on the opposite strand); (E) enhancer RNA (They expressed as uni- or bidirectional transcripts); (F) miRNA host gene .

Figure 3

lncRNA research strategies and methods. A. New species identification: Using methods, such as RNA-seq et al could discover new kinds of lncRNAs; B. Subcellular localization: FISH could help to analyze the location of target lncRNAs; C. Gain or loss of function: over-expression or knock down the lncRNA by lentivirus, shRNA or siRNA could help to learn the basic function of lncRNAs in cell; D. Molecular interaction: Using methods like RIP et al could analyze the interactions among RNA, DNA and protein; E. Bioinformatics analysis: Various kinds of databases could help to learn about the interested lncRNAs.

Figure 2

The working mechanisms of lncRNAs. The present known working mechanisms of lncRNAs might be only a part of its all functions, just like several hubbles among all blowing group. A. ceRNA function of lncRNA: circRNA compete binding with miRNA to prevent miRNA binding with target mRNAs; B. Enhancer on/off: lncRNAs transcribed from an enhancer region interact with enhancer-promoter contact to inhibit the transcription of the protein-coding gene; C. lncRNAs acting as scaffold linking different proteins interaction; D. lncRNAs binding with proteins to prevent their actions; E. lncRNAs recruiting proteins, such as chromatin- modifying complexes to specific target sites in the genome; F. lncRNAs loop formation and transcription of the associated gene; G. lncRNA transcripts evicting proteins from chromatin, such as pancRNA prevent DNMT from methylating DNA in their promoter region, thereby ensuring mRNA transcription; H. Stabilizing of mRNA: lncRNA recruiting proteins to preventing degradation.