The decalog of long non-coding RNA involvement in cancer diagnosis and monitoring

Abstract

Long non-coding RNAs (lncRNAs) are transcripts without protein-coding capacity; initially regarded as "transcriptional noise", lately they have emerged as essential factors in both cell biology and mechanisms of disease. In this article, we present basic knowledge of lncRNA molecular mechanisms, associated physiological processes and cancer association, as well as their diagnostic and therapeutic value in the form of a decalog: (1) Non-coding RNAs (ncRNAs) are transcripts without protein-coding capacity divided by size (short and long ncRNAs), function (housekeeping RNA and regulatory RNA) and direction of transcription (sense/antisense, bidirectional, intronic and intergenic), containing a broad range of molecules with diverse properties and functions, such as messenger RNA, transfer RNA, microRNA and long non-coding RNAs. (2) Long non-coding RNAs are implicated in many molecular mechanisms, such as transcriptional regulation, post-transcriptional regulation and processing of other short ncRNAs. (3) Long non-coding RNAs play an important role in many physiological processes such as X-chromosome inactivation, cell differentiation, immune response and apoptosis. (4) Long non-coding RNAs have been linked to hallmarks of cancer: (a) sustaining proliferative signaling; (b) evading growth suppressors; (c) enabling replicative immortality; (d) activating invasion and metastasis; (e) inducing angiogenesis; (f) resisting cell death; and (g) reprogramming energy metabolism. (5) Regarding their impact on cancer cells, lncRNAs are divided into two groups: oncogenic and tumor-suppressor lncRNAs. (6) Studies of lncRNA involvement in cancer usually analyze deregulated expression patterns at the RNA level as well as the effects of single nucleotide polymorphisms and copy number variations at the DNA level. (7) Long non-coding RNAs have potential as novel biomarkers due to tissue-specific expression patterns, efficient detection in body fluids and high stability. (8) LncRNAs serve as novel biomarkers for diagnostic, prognostic and monitoring purposes. (9) Tissue specificity of lncRNAs enables the development of selective therapeutic options. (10) Long non-coding RNAs are emerging as commercial biomarkers and therapeutic agents.

The Long Non-coding RNA HIF1A-AS2 Facilitates the Maintenance of Mesenchymal Glioblastoma Stem-like Cells in Hypoxic Niches

“…Although thousands of lncRNAs have been discovered to date, very little is known about their mode of action and possible role in the regulation of cancer-related processes. The positive correlation of bidirectional sense/antisense transcription is in accord with numerous studies showing that antisense RNAs can regulate their neighboring genes in a cis - mode (Kunej et al, 2014). Here we have shown that although HIF1A-AS2 expression responds to hypoxic stress, it had no effect on the expression of its neighboring gene in sense orientation – HIF1A.…”

Long non-coding RNA HULC as a novel serum biomarker for diagnosis and prognosis prediction of gastric cancer

“…Mounting evidence shows that lncRNAs play important roles in a large range of biological processes and diseases, especially in cancer biology [9]. Compared with protein biomarkers expressed in multiple tissue types, lncRNAs often exhibit a tissue-specific expression pattern and can be detected easily in body fluids due to high stability, making them ideal biomarkers [10]. Some lncRNAs, such as HOTAIR [11, 12], H19 [2, 13], GAPLINC [14], ANRIL [15], are reported to be oncogenic molecules in GC.…”

Integrated analysis of long non-coding RNA competing interactions reveals the potential role in progression of human gastric cancer

“…lncRNA is the functional end-product, and the level of lncRNA expression correlates directly with the level of the active molecule. Thus, the use of lncRNAs in diagnostics has intrinsic advantages over the use of protein-coding RNAs (4). In addition, lncRNAs show greater tissue specificity compared to miRNAs and protein-coding mRNAs, making them attractive in the search for novel diagnostic and prognostic cancer biomarkers (5).…”