Long Non-coding RNAs and Their Clinical Relevance in Cancer and Cancer Therapy

Long non-coding RNAs (lncRNAs) are clinically relevant in at least two major ways: as biomarkers for cancer or carcinogenesis and as actual targets for cancer therapy.

LncRNAs as biomarkers for cancer and carcinogenesis

LncRNAs can be biomarkers for cancer or carcinogenesis, and can yield insight into possible sensitivity or resistance to potential anti-cancer therapies. A well-known example includes the FDA-approved PROGENSA PCA3 assay testing in urinary samples used as part of the screening paradigm for prostate cancer. This is one demonstration of a testable form of lncRNA that exists with sufficient stability in a non-invasive biological sample, highlighting the key attributes of stability and ability to be assayed of a viable biomarker.

LncRNAs as targets for cancer therapy

A number of lncRNA genes have been found to be expressed at elevated levels which correlate with various cancers. To investigate a possible causal connection, there are several options to reduce or knockout expression in vivo, where the technology has already been proven to be effective in in vitro or cell culture settings. These approaches include (Gutschner et al.,2018):

  • siRNAs that are complementary to lncRNA which takes advantage of the RISC/argonaute system to degrade the target molecule
  • anti-sense oligos (ASOs), refined with chemical modifications to enhance activity or stability, which have been demonstrated to function by targeting lncRNAs to the endogenous RNase H systems for destruction
  • the use of targeting ribozymes, deoxyribozymes, or CRISPR/Cas9-derived technologies which have been proposed for silencing lncRNA.

The evolving field of RNA biology and lncRNA

Image credit: Parasramka et al. (2016)

Once relegated to the ‘junk’ DNA category, large segments of the genome and their associated transcripts have long been ignored, or thought of as unimportant. Only a few Continue reading