The implication of long non-coding RNAs in the diagnosis, pathogenesis and drug resistance of pancreatic ductal adenocarcinoma and their possible therapeutic potential

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the lethal malignancies with the lowest median and overall survival rate among all human malignancies. The major problems with the PDAC are the late diagnosis, metastasis, and acquired resistance to chemotherapeutic agents in the clinic. Over the last decade, the long non-coding RNAs (lncRNAs) have been discovered and occupies a significantly large proportion of the human genome. Recent studies have proved that lncRNAs can play a crucial role in the majority of key cellular processes involved in the maintenance of cellular homeostasis by regulating various molecular mechanisms. The deregulation of lncRNAs has been associated with various chronic diseases including human malignancies. Several lncRNAs have tumor-specific expression making them an ideal and excellent target for designing the novel therapeutic strategies against human malignancies. We have discussed how lncRNA expression can be used for the diagnosis and prognosis of PDAC. The current review discusses the potential role and molecular mechanism of lncRNA in regulating the prominent hallmarks of cancer including abnormal growth, survival, metastasis, and drug-resistance in PDAC. Importantly, we also highlight the possible application of various therapeutic strategies including small interfering RNA, CRISPR-Cas9, antisense oligonucleotides, locked nucleic acid Gapmers, small molecules, aptamers, lncRNA promoter to target the lncRNA as a novel and viable options for treatment of PDAC.

Keywords: Antisense oligonucleotides; CRISPR-Cas9; KRAS; Long non-coding RNA (lncRNA); Pancreatic ductal adenocarcinoma (PDAC).