• Long non-coding RNAs, potential targets in cancer treatment
  • Behdokht Fathi Dizaji,1,*
    1. Department of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran


  • Introduction: Long non-coding RNAs have been recognized as crucial regulators of gene expression and divers biological processes. Their abnormal expression contributes to various diseases including cancer, conferring lncRNAs great potential as therapeutic targets in cancer.
  • Methods: Related articles to the subject by using databases such as pubmed and sciencedirect was extracted and scrutinized.
  • Results: Numerous strategies including, suppression of onco-genic lncRNAs, alternation of their epigenetic effects, restoration of down -regulated or lost lncRNAs, as well as LncRNAs regulatory elements and expression patterns have successfully been recruited to therapeutically target lncRNAs in cancer treatment. In lung cancer, RNA destabilizing Elements (RDE) was integrated into the locus of MALAT1 (Metastasis-Associated Lung Adenocarcinoma Transcript 1) by utilizing Zinc finger nucleases (ZFNs) in human cancer cells.1000 fold decreased expression was observed in stable knock-out colons. The knock-down of MALAT1 with a plasmid vector encoding short hairpin RNA (shRNAs) to target MALAT1 in cervical cancer, prevented metastasis and invasion in vitro and in vivo. Long Noncoding RNA–BLR suppression by siRNAs in gastric cancer reduced cell proliferation, suppressed cell migration and invasion of gastric cancer cells. siRNA knock-down of a lncRNA, second chromosome locus associated with prostate-1(SChLAP1) reduced cell proliferation and invasiveness. Targeting the SCAMP1/miR-499a-5p/LMX1A/NLRC5 pathway via Short hairpin RNAs can be a new therapeutic approach for glioma treatment. In addition, (ellipticine), which is a drug, was discovered that up-regulates the BDNF transcription. Moreover, chemical modifications of nucleic acids to improve their pharmacological properties have been carried out as well as the evaluation of the safe and efficient Systemic delivery of therapeutics to the target organs or cells. Nanocarriers such as Viral vectors, lipid-based, polymeric and inorganic particle-based vectors, inorganic nanocarriers, aptamer-guided RNAi, cell Penetrating Peptides (CPPs) and exosomes, might be as approaches to deliver lncRNAs targeting therapeutics to the site of interest. ASOs can be taken up freely by cells in¬¬ vivo. Lentiviral frame plasmids were built as vectors for RNAi which targeted HOTAIR in Vitro and in Vivo. In a mouse model of ovarian cancer, the up-regulated lncRNA ceruloplasmin (NRCP) was silenced using a phosphocholine derived (DOPC) nanoliposome containing siRNA. lncRNAs within exosomes which was presented to target cells, remained functional. Thus, are appropriate to retrieve the expression of tumor suppressive lncRNAs in tumor cells.
  • Conclusion: Long non-coding therapeutic targeting approaches beside efficient and safe systematic delivery of the therapeutics in cancer therapy are in the very beginning state and the experience with therapeutic targeting of lncRNAs is very little. Only one clinical trial (www.clinicaltrials.gov, NCT02641847) involving lncRNAs have been reported. Therefore, the expansion of our knowledge about lncRNAs and doing comprehensive research is essential.
  • Keywords: Long non-coding RNAs - Therapeutic targets - Systematic delivery - Cancer treatment