Non-coding RNAs as therapeutic targets in cancer and its clinical application

Abstract

Cancer genomics has led to the discovery of numerous oncogenes and tumor suppressor genes that play critical roles in cancer development and progression. Oncogenes promote cell growth and proliferation, whereas tumor suppressor genes inhibit cell growth and division. The dysregulation of these genes can lead to the development of cancer. Recent studies have focused on non-coding RNAs (ncRNAs), including circular RNA (circRNA), long non-coding RNA (lncRNA), and microRNA (miRNA), as therapeutic targets for cancer. In this article, we discuss the oncogenes and tumor suppressor genes of ncRNAs associated with different types of cancer and their potential as therapeutic targets. Here, we highlight the mechanisms of action of these genes and their clinical applications in cancer treatment. Understanding the molecular mechanisms underlying cancer development and identifying specific therapeutic targets are essential steps towards the development of effective cancer treatments.

Keywords: Cancer; Clinical application; Non-coding RNA; Therapeutic targets.

Graphical abstract

Fig. 1

Nine types of non-coding RNAs (ncRNAs) are synthesized in different ways. In the nucleus, RNA polymerase (Pol) II transcribes microRNAs (miRNA) primary transcripts, which is then cleaved into pre-miRNA. Esportin-5 transports pre-miRNA from the nucleus to the cytoplasm, where it is further processed by RNA Pol III into mature miRNA. PIWI-associated RNA (piRNA) genes are transcribed by RNA Pol II to generate small nucleotide sequences, which serve as the primary synthesis of piRNA. Circular RNA (circRNA) is generated through a unique alternative splicing process called backsplicing, which results in a closed-loop structure with a back-splicing junction site. Long non-coding RNAs (lncRNAs) are transcribed from various regions of mRNAs, including the anti-sense strand, promoter region, intron region, and intergenic region. Short hairpin RNA (shRNA) is produced in the nucleus from DNA, and the Dicer enzyme cleaves it into small interfering RNA (siRNA) in the cytoplasm. Transfer RNA (tRNA) genes on DNA molecules are transcribed into tRNA precursors, which are then processed into mature tRNA. rDNAs are transcribed by RNA Pol I to generate pre-rRNAs that undergo several modifications and processing steps, resulting in mature 18S, 5.8S and 28S rRNAs. Except for U6, which is transcribed by RNA Pol III, all other small nuclear RNAs (snRNAs) are transcribed by RNA Pol II. Most small nucleolar RNAs (snoRNAs) are mainly located in the intron region of genes transcribed by RNA Pol II.

Fig. 2

Circular RNAs (circRNAs) associated with various types of cancer. Orange font represents oncogenes, and blue font represents tumor suppressor genes.

Fig. 3

Long non-coding RNAs (lncRNAs) associated with various types of cancer. Orange font represents oncogenes, and blue font represents tumor suppressor genes.

Fig. 4

microRNAs (miRNAs) associated with various types of cancer. Orange font represents oncogenes, and blue font represents tumor suppressor genes.

Fig. 5

Impact of three types of non-coding RNA (ncRNA) on tumor immunity.