Cancer research with non-coding RNA

Abstract

Cancer research is not limited to medical research; it expands over several disciplines, incorporating molecular bioscience at both the macro and micro levels. All stages and aspects of cells, from development and differentiation, apoptosis, cell adhesion and many more, are research fields with a connection to cancer. Cancer research in itself is the research of cancer cures. Recently, not only cancer but also bioscience research has surfed on the new wave of RNA knowledge. Most of those RNAs are non-protein-coding RNAs and are connected to cell development and differentiation, and thereby with cancer differentiation and treatment. Here we would like to introduce the latest in cancer research that has emerged from the field of molecular biology research.

Figure 1

There are various kinds of small interfering RNA (siRNA) that cause gene expression suppression. Most commonly used is synthetic siRNA, and the siRNA expression vector. The bidirectional 2‐promoter expression vector has two RNA polymerase III promoters located on both sides of the siRNA sequence, which is complementary to the sense and antisense transcript. The short hairpin RNA (shRNA) expression vector has one RNA polymerase III promoter at one side of a sequential arrayed sense and antisense in order to form a hairpin structure. Transfected or expressed siRNA is captured by the RNA‐induced silencing complex (RISC) where one strand is removed. The guide RNA transcript and RISC complex are then ready to recognize and cleave a target mRNA. dsRNA, double‐stranded RNA.

Figure 2

Non‐coding RNA biogenesis. Small interfering RNA (siRNA), trans‐acting siRNA (tasiRNA) and repeat‐associated small interfering RNA (rasiRNA) all derive from long double‐stranded RNA transcripts. siRNA comes from endogenous or exogenous (e.g. viral) sources through processing by Dicer into ∼21–22mer long transcripts. tasiRNA uses parts from the biogenesis of both siRNA and micro RNA (miRNA), and direct cleavage of endogenous cognate mRNAs in trans and has only been found in plants and nematodes. rasiRNA originates from long repeat double‐stranded RNA transcripts and therefore target repeats, and is involved in the establishment of heterochromatin in repetitive elements. The rasiRNA effector complex is the RNA‐induced initiation of transcriptional silencing complex (RITS). Small scan RNA (scnRNA) is likely to use some parts of miRNA and siRNA biogenesis as Twi, an Argounaute protein, is required together with the scnRNA for H3K9 methylation and subsequent elimination of DNA. RISC, RNA‐induced silencing complex.

Figure 3

Micro RNA (miRNA) originates from long primary hairpin transcripts transcribed from genomic DNA by RNA polymerase II. These primary transcripts (pri‐miRNA) are cleaved by Drosha (limited to animals, plants use DCL1 instead) plus cofactors to yield pre‐miRNA with a ∼50–70‐nucleotide‐long hairpin loop structure. This pre‐miRNA is exported by Exportin‐5 to the cytoplasm and cleaved by Dicer to yield the 18–24‐nucleotide‐long miRNA. When the miRNA is incorporated into the effector complex, RNA‐induced silencing complex (RISC), one strand is degraded and the remaining strand is used as guide transcript. A partial match to the target induces translational depression whereas a complete match induces cleavage of the target mRNA. Plant miRNA tend to have a higher grade of complimentary to the target sequence and therefore induce cleavage to a higher degree.