Long non-coding RNAs: From disease code to drug role

Abstract

Enormous studies have corroborated that long non-coding RNAs (lncRNAs) extensively participate in crucial physiological processes such as metabolism and immunity, and are closely related to the occurrence and development of tumors, cardiovascular diseases, nervous system disorders, nephropathy, and other diseases. The application of lncRNAs as biomarkers or intervention targets can provide new insights into the diagnosis and treatment of diseases. This paper has focused on the emerging research into lncRNAs as pharmacological targets and has reviewed the transition of lncRNAs from the role of disease coding to acting as drug candidates, including the current status and progress in preclinical research. Cutting-edge strategies for lncRNA modulation have been summarized, including the sources of lncRNA-related drugs, such as genetic technology and small-molecule compounds, and related delivery methods. The current progress of clinical trials of lncRNA-targeting drugs is also discussed. This information will form a latest updated reference for research and development of lncRNA-based drugs.

Long non‑coding RNA SLC25A25‑AS1 exhibits oncogenic roles in non‑small cell lung cancer by regulating the microRNA‑195‑5p/ITGA2 axis

“…Recently, lncRNAs have gained increasing attention in targeted therapy of human cancer ( 38 – 40 ). At present, targeting lncRNAs can be achieved through multiple different approaches, such as transcription block, degradation and gene-editing technology ( 41 , 42 ). Furthermore, abolishment of the interaction between lncRNAs and their downstream targets utilizing competitive binding is an additional method targeting lncRNAs ( 43 ).…”

Prostate cancer resistance leads to a global deregulation of translation factors and unconventional translation of long non-coding RNAs

“…Our data corroborates previous studies linking some of our candidate lncRNAs to PCa (Gao et al 2019;Zhang et al 2016b;Wan et al 2015) and highlighting potential novel roles for several others. Using lncRNAs for drug resistant PCa early detection and treatment represents an avenue of high interest due to their highly restricted spatio-temporal expression patterns and their relative ease of targeting, for example using specific anti-sense oligonucleotides (Nandwani et al 2020;Chen et al 2020b;Bonetti and Carninci 2017). While research on cancer therapies targeting lncRNAs has not yet reached clinical trials, several studies have shown promise and widening the knowledge on lncRNAs of potential clinical importance therefore constitutes a priority for the coming years.…”

Novel long noncoding RNA Linc1749808 promotes hepatocellular carcinoma metastasis by negatively regulating miR-206

“…Abnormally expressed lncRNAs participate in the development, invasion and metastasis of HCC through different pathways and different mechanisms [21,22]. For example, Linc-KILH potentiates EMT through the KRT19 phosphorylation/Notch1 pathway to promote liver cancer metastasis [23].…”