ncRNA-Encoded Peptides or Proteins and Cancer

Abstract

Non-coding RNAs (ncRNAs) are unique RNA transcripts that have been widely identified in the eukaryotic genome and have been shown to play key roles in the development of many cancers. However, the rapid development of genome-wide translation profiling and ribosome profiling has revealed that a small number of small open reading frames (sORFs) within ncRNAs actually have peptide- or protein-coding potential. The peptides or proteins encoded by ncRNA (HOXB-AS3, encoded by long ncRNA [lncRNA]; FBXW7-185aa, PINT-87aa, and SHPRH-146aa, encoded by circular RNA [circRNA]; and miPEP-200a and miPEP-200b, encoded by primary miRNAs) have been shown to be critical players in cancer development and progression, through effects upon the regulation of glucose metabolism, the epithelial-to-mesenchymal transition, and the ubiquitination pathway. In this review, we summarize the reported peptides or proteins encoded by ncRNAs in cancer and explore the application of these peptides or proteins in the development of anti-tumor drugs and the identification of relevant therapeutic targets and tumor biomarkers.

Keywords: cancer; circRNA; lncRNA; miRNA; ncRNA; peptide; protein.

Figure 1

The Functions of lncRNAs Are Involved in Cancer Mainly in Two Aspects: As RNA Molecules and by Encoding Peptides or Proteins (A–H) lncRNAs exert their functions as RNA molecules in chromatin remodeling (A), transcriptional activation (B), transcriptional suppression (C), RNA editing (D), RNA degradation (E), translational regulation (F), RNA splicing (G), and miRNA sponge (H). (I) lncRNA HOXB-AS3 encodes a 53-aa peptide that inhibits cancer growth and metabolism reprogramming by blocking the binding of hnRNP A1 to the sequences flanking PKM exon 9 to regulate PKM splicing and induce PKM1 isoform formation. ADAR, adenosine deaminase acting on RNA; PRC2, polycomb repressive complex 2; SR, splicing regulator; STAU1, staufen 1; TF, transcription factor.

Figure 2

The Functions of circRNAs Are Involved in Cancer Mainly in Two Aspects: As RNA Molecules and by Encoding Peptides or Proteins (A–E) circRNAs, as RNA molecules, regulate parental gene transcription (A), protein localization (B), miRNA functions as miRNA sponge (C), protein activity (D), and alternative splicing (E). (F) circ-FBXW7 and circ-SHPRH encode FBXW7-185aa and SHPRH-146aa to induce oncoprotein C-MYC and PCNA ubiquitination degradation, respectively, and circPINTexon2 encodes PINT-87aa to inhibit transcriptional elongation of PAF1 downstream oncogenes. IRES, internal ribosome entry sites; m6A, N6-methyladenosine; RBP, RNA-binding protein; ub, ubiquitin.

Figure 3

The Functions of pri-miRNAs Are Involved in Cancer Mainly in Two Aspects: As Mature miRNA Molecules and by Encoding Peptides or Proteins (A) pri-miRNAs are processed to become mature miRNAs that inhibit target gene expression. (B) pri-miRNAs pri-miR-200a and pri-miR-200b encode 187-aa miPEP-200a protein and 54-aa miPEP-200b peptide to inhibit cancer migration and EMT, respectively. AGO2, Argonaute; DGCR8, DiGeorge syndrome critical region 8; EMT, epithelial-to-mesenchymal transition; RISC, RNA-induced silencing complex; TRBP, TAR RNA-binding protein.