bims-micpro 2023-06-25 papers

Issue of 2023‒06‒25
two papers selected by
Thomas Farid Martínez
University of California, Irvine

Protein Sci. 2023 Jun 23. e4708

Shining a Light on the Dark Proteome: Non-Canonical Open Reading Frames and their Encoded MiniProteins as a New Frontier in Cancer Biology.

Zoe Posner, Ian Yannuzzi, John R Prensner.

In the decades following the discovery that genes encode proteins, scientists have tried to exhaustively and comprehensively characterize the human genome. Recent advances in computational methods along with transcriptomic and proteomic techniques have now shown that historically non-coding genomic regions may contain non-canonical open reading frames (ncORFs), which may encode functional miniproteins or otherwise exert regulatory activity through coding-independent functions. Increasingly, it is clear that these ncORFs may play critical roles in major human diseases such as cancer. In this review, we summarize the history and current progress of ncORF research and explore the known functions of ncORFs and the miniproteins they may encode. We particularly highlight the emerging body of evidence supporting a role for ncORFs and miniproteins contributions in cancer. Finally, we provide a blueprint for high-priority areas of future research for ncORFs in cancer, focusing on ncORF detection, functional characterization, and therapeutic intervention. This article is protected by copyright. All rights reserved.

Keywords: Miniprotein; Non-coding genome; Open reading frame; cancer

DOI: https://doi.org/10.1002/pro.4708

PLoS One. 2023 ;18(6): e0287133

Peptide encoded by lncRNA BVES-AS1 promotes cell viability, migration, and invasion in colorectal cancer cells via the SRC/mTOR signaling pathway.

Weiwei Zheng, Yingchang Guo, Guangtan Zhang, Junwei Bai, Yucheng Song, Xiaofei Song, Qinhui Zhu, Xuebin Bao, Gang Wu, Chao Zhang.

Long non-coding RNAs (lncRNAs) have been revealed to harbor open reading frames (ORFs) that can be translated into small peptides. The peptides may participate in the pathogenesis of colorectal cancer (CRC). Herein, we investigated the role of a lncRNA BVES-AS1-encoded peptide in colorectal tumorigenesis. Through bioinformatic analysis, lncRNA BVES-AS1 was predicted to have encoding potential and to be associated with poor prognosis of patients with CRC. In CRC cells, BVES-AS1 was validated to encode a 50-aa-length micro-peptide, named BVES-AS1-201-50aa, through a western blotting method. BVES-AS1-201-50aa enhanced cell viability and promoted the migratory and invasive capacities of HCT116 and SW480 CRC cells in vitro, validated via CCK-8 assay and transwell assay, respectively. Immunofluorescence assay showed that BVES-AS1-201-50aa increased the expression of proliferating cell nuclear antigen (PCNA) and matrix metalloproteinase 9 (MMP9) in CRC cells. We further verified that BVES-AS1-201-50aa targeted and activated the Src/mTOR signaling pathway in CRC cells by co-immunoprecipitation (Co-IP) experiment, qualitative proteomic analysis, and western blotting. Our findings demonstrated that BVES-AS1 could encode a micro-peptide, which promoted CRC cell viability, migration, and invasion in vitro. Our current work broadens the diversity and breadth of lncRNAs in human carcinogenesis.

DOI: https://doi.org/10.1371/journal.pone.0287133