Long non-coding RNAs (lncRNAs) are a class of RNAs that do not code for proteins and are typically greater than 200 nucleotides in length. Studies have shown that lncRNAs are quite complex in function and play an important role in various biological processes such as development, differentiation, proliferation, metastasis, apoptosis, stem cell pluripotency, and DNA damage. Therefore, those non-coding fragments in human genes are also vital and not the so-called “transcriptional noise”.

 

RNA Sequencing Pulls Insights in LncRNA

A growing number of genetic studies have linked lncRNA gene aberrations to the development of human diseases. However, a protein-centric view of human disease does not fully capture the complexity of the molecular pathogenesis regulated by lncRNAs. Therefore, the help of lncRNA-Seq data is required in the discovery, characterization and analysis of lncRNAs and functions. RNA-Seq is not dependent on reference genome annotations or sequences and can accurately detect expression levels over a wide dynamic range, which is a very important and effective means to characterize and quantify non-coding RNAs (ncRNAs).

 

Next-generation sequencing (NGS) technology provides a platform to generate sequencing data in less time and at a lower cost, allowing the production of high-throughput RNA-seq data for in-depth study of all possible aspects of the transcriptome. Long read sequencing technology, a single-molecule real-time sequencing strategy, breaks the limits of read length, GC bias, and amplification error by enabling direct sequencing of naturally long transcripts without the need for a cDNA preparation step.

 

On the other hand, whole transcriptome sequencing can not only characterize lncRNAs and circRNAs in samples, but also perform a global analysis of small RNAs, enrich and identify their target genes, and help construct and map ncRNA and mRNA (competitive endogenous RNA, eRNA) regulatory networks to enable the study of relevant physiological and pathological processes.

 

The Relationship Between LncRNAs and Diseases

Unlike other ncRNAs such as miRNAs, lncRNAs are large and complex. lncRNAs’ molecular mechanisms mainly include (1) binding directly to DNA or transcription factors to achieve regulation of gene expression through translational processes; (2) targeting mRNAs, miRNAs or proteins to regulate post-translational stability and activity; (3) participating in chromatin remodeling to repress or active gene expression.

 

The relationship between lncRNAs and diseases is well established, especially in chronic disorders. However, cancer is one of the most intensively studied diseases associated with lncRNAs. With the increasing abundance and diversity of identified oncogenic and tumor suppressor lncRNAs, it suggests that they can serve as potential drug targets and biomarkers in cancer research. For example, NEAT1, a well-studied lncRNA, is closely associated with chemoresistance in various cancers.

 

The functional role of lncRNAs in a variety of neuropathic pain and neurological disorders is increasingly recognized. Multiple lncRNAs related to synapse formation and neuronal survival (e.g., tncRNA and SNHG1) were identified in Parkinson’s disease by sequencing and differential expression analysis. And clusters of lncRNAs regulating neuronal apoptosis, such as MALAT1, H19 and BDNF-AS, were present in Alzheimer’s disease studies. In other chronic diseases like diabetes, global sequencing analysis has revealed that lncRNAs are associated with pancreatic β-cell disease, insulin resistance and other complications. As the information about lncRNAs and their role in disease continues to be decoded, lncRNAs not only have become important targets for studying pathogenesis and progression mechanisms, but also have significant potential for developing innovative biomarkers and therapeutic approaches.