Novel applications of viruses in noncoding RNA therapy for gastrointestinal cancers

BACKGROUND AND OBJECTIVESRespecting the high mortality rate of gastrointestinal (GI) cancers, there is an urgent need to propose novel therapeutic approaches to overcome GI cancers. Utilization of viruses in regard to realign ncRNA transcription to cease tumorigenesis in addition to their capability of coding siRNAs and miRNAs to silence oncogenes highlights their inimitable competence as anti-tumor vectors. Moreover, intrinsic features of viruses as drastic immunogens to induce immune response along with unsurpassed ability of oncolytic viruses to target specific tumors represents them as potent anti-cancer vectors. In this review, we will discuss novel applications of viruses in ncRNA based GI cancers therapy as a treatment method capable of rectifying deficiencies of traditional treatments.MATERIALS AND METHODSTo conduct this research, we studied articles regarding ncRNA therapy, gastrointestinal cancers and viral vectors on PubMed and Google Scholar.RESULTS AND DISCUSSIONImplementation of viruses in ncRNA therapy is a multilateral combat strategy against GI cancers. Besides their ability in coding ncRNAs, direct lysis of virus-infected tumor cells leads to the release of tumor antigens, altering innate immune system as well as leaving the tumor microenvironment exposed. Utilization of ncRNA therapy in combination with immunotherapy is facilitated thanks to viral vectors, as monoclonal antibodies can be fused to viral capsids. Adenoviruses are outstanding viral vectors utilized in ncRNA therapy as they are capable of coding siRNAs to silence PI۳K gene, which results in apoptosis of gastric cancer (GC) cells and inhibits proliferation. Lentiviruses are RNA viruses inducing down-regulation of synuclein with RNA interference (RNAi) as well as a decline in tau phosphorylation with siRNAs. Furthermore, Semliki Forest virus (SFV) is an alphavirus with miRNAs capable of tumor targeting and tumor growth inhibition.CONCLUSIONApplication of viruses in ncRNA Therapy has exhibited promising results. However, low efficiency of viral vectors in tumor mass penetration, antiviral immune response of host and instability of ncRNAs should be addressed. Nevertheless, ncRNA therapy and oncolytic viruses will soon become an integral part of GI cancers therapy.

Keywords:

gastrointestinal cancers , ncRNA therapy , viral vectors , gene therapy , oncolytic viruses