Small non-coding RNAs as diagnostic, prognostic and predictive biomarkers of gynecological cancers: an update DOI
Marios A. Diamantopoulos, Panagiotis G. Adamopoulos, Andreas Scorilas

et al.

Expert Review of Molecular Diagnostics, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 17

Published: Oct. 10, 2024

Introduction Non-coding RNAs (ncRNAs) comprise a heterogeneous cluster of RNA molecules. Emerging evidence suggests their involvement in various aspects tumorigenesis, particularly gynecological malignancies. Notably, ncRNAs have been implicated as mediators within tumor signaling pathways, exerting influence through interactions with or proteins. These findings further highlight the hypothesis that constitute therapeutic targets and point out clinical potential stratification biomarkers.

Language: Английский

Upstream open reading frames: new players in the landscape of cancer gene regulation DOI Creative Commons
Anwesha Dasgupta, John R. Prensner

NAR Cancer, Journal Year: 2024, Volume and Issue: 6(2)

Published: April 8, 2024

The translation of RNA by ribosomes represents a central biological process and one the most dysregulated processes in cancer. While is traditionally thought to occur exclusively protein-coding regions messenger RNAs (mRNAs), recent transcriptome-wide approaches have shown abundant ribosome activity across diverse stretches transcripts. common type this kind occurs gene leader sequences, also known as 5' untranslated (UTRs) mRNA, that precede main coding sequence. Translation these upstream open reading frames (uORFs) now upwards 25% all genes. With functions from regulation microprotein generation, uORFs are rapidly igniting new arena cancer biology, where they linked genetics, signaling, tumor-immune interactions. This review focuses on contributions their associated 5'UTR sequences biology.

Language: Английский

Citations

7
Interdisciplinary Approaches to Leverage Biomarker Discovery for Cancer Treatment DOI
Fatemeh Khatami, Nima Rezaei

Interdisciplinary cancer research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

0
Shining a light on the dark proteome: Non‐canonical open reading frames and their encoded miniproteins as a new frontier in cancer biology DOI Creative Commons
Zoe Posner, Ian Yannuzzi, John R. Prensner

et al.

Protein Science, Journal Year: 2023, Volume and Issue: 32(8)

Published: June 24, 2023

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

Language: Английский

Citations

12
High-throughput discovery of inhibitory protein fragments with AlphaFold DOI Creative Commons
Andrew Savinov, Sebastian Swanson, Amy E. Keating

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(6)

Published: Feb. 3, 2025

Peptides can bind to specific sites on larger proteins and thereby function as inhibitors regulatory elements. Peptide fragments of are particularly attractive for achieving these functions due their inherent potential form native-like binding interactions. Recently developed experimental approaches allow high-throughput measurement protein fragment inhibitory activity in living cells. However, it has thus far not been possible predict de novo which the many targets, let alone act inhibitors. We have a computational method, FragFold, that employs AlphaFold full-length manner. Applying FragFold thousands tiling across diverse revealed peaks predicted along each sequence. Comparisons with measurements establish our approach is sensitive predictor function: Evaluating from known protein–protein interaction interfaces, we find 87% by mode. Across full sequences, 68% FragFold-predicted match experimentally measured peaks. Deep mutational scanning experiments support modes uncover superior peptides high throughput. Further, able previously unknown modes, explaining prior genetic biochemical data. The success rate demonstrates this should be broadly applicable discovering proteomes.

Language: Английский

Citations

0
Noncanonical microprotein regulation of immunity DOI

Cydney Nichols,

Van Anh Do-Thi, Daniel Peltier

et al.

Molecular Therapy, Journal Year: 2024, Volume and Issue: 32(9), P. 2905 - 2929

Published: May 11, 2024

Language: Английский

Citations

2
High-throughput computational discovery of inhibitory protein fragments with AlphaFold DOI Creative Commons
Andrew Savinov, Sebastian Swanson, Amy E. Keating

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 20, 2023

Abstract Peptides can bind to specific sites on larger proteins and thereby function as inhibitors regulatory elements. Peptide fragments of are particularly attractive for achieving these functions due their inherent potential form native-like binding interactions. Recently developed experimental approaches allow high-throughput measurement protein fragment inhibitory activity in living cells. However, it has thus far not been possible predict de novo which the many targets, let alone act inhibitors. We have a computational method, FragFold, that employs AlphaFold full-length manner. Applying FragFold thousands tiling across diverse revealed peaks predicted along each sequence. Comparisons with measurements establish our approach is sensitive predictor function: Evaluating from known protein-protein interaction interfaces, we find 87% by mode. Across full sequences, 68% FragFold-predicted match experimentally measured peaks. Deep mutational scanning experiments support modes uncover superior peptides high throughput. Further, able previously unknown modes, explaining prior genetic biochemical data. The success rate demonstrates this should be broadly applicable discovering proteomes. Significance Statement regulate interactions methods massively parallel fragment-based inhibition vivo . lacked comparable how they bind. Here report new approach, leverages predictions – tackle problems at scale. successful predicting structures functions. This stands enable proteome-wide discovery aid interpretation activity. Classification Biological Sciences / Biophysics Computational Biology

Language: Английский

Citations

4
Advances and opportunities in methods to study protein translation - A review DOI

Dejiu Zhang,

Yanyan Gao, Lei Zhu

et al.

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 259, P. 129150 - 129150

Published: Jan. 1, 2024

Language: Английский

Citations

1
Exploring the Dark Matter of Human Proteome: Emerging Role of Non-canonical Open Reading Frame (ncORF) in Cancer Diagnosis, Biology, and Therapy DOI Open Access
Anni Ge,

Curtis Chan,

Xiaolong Yang

et al.

Published: June 28, 2024

Cancer develops from abnormal cell growth in the body, causing significant mortalities every year. To date, potent therapeutic approaches have been developed to eradicate tumor cells, but intolerable toxicity and drug resistance can occur treated patients, limiting efficiency of existing treatment strategies. Therefore, searching for novel genes critical cancer progression response is urgently needed successful therapy. Recent advances bioinformatic proteomic techniques allowed identification a category peptides encoded by non-canonical open reading frames (ncORFs) historically non-coding genomic regions. Surprisingly, many ncORFs express functional microproteins that play vital role human cancers. In this review, we provide comprehensive description different ncORF types with coding capacity technological methods discovering among genomes. We also summarize diagnostic prognostic value these as well their carcinogenic underestimated potential targets.

Language: Английский

Citations

1
Exploring the Dark Matter of Human Proteome: The Emerging Role of Non-Canonical Open Reading Frame (ncORF) in Cancer Diagnosis, Biology, and Therapy DOI Open Access
Anni Ge,

Curtis Chan,

Xiaolong Yang

et al.

Cancers, Journal Year: 2024, Volume and Issue: 16(15), P. 2660 - 2660

Published: July 26, 2024

Cancer develops from abnormal cell growth in the body, causing significant mortalities every year. To date, potent therapeutic approaches have been developed to eradicate tumor cells, but intolerable toxicity and drug resistance can occur treated patients, limiting efficiency of existing treatment strategies. Therefore, searching for novel genes critical cancer progression response is urgently needed successful therapy. Recent advances bioinformatics proteomic techniques allowed identification a category peptides encoded by non-canonical open reading frames (ncORFs) historically non-coding genomic regions. Surprisingly, many ncORFs express functional microproteins that play vital role human cancers. In this review, we provide comprehensive description different ncORF types with coding capacity technological methods discovering among genomes. We also summarize carcinogenic such as pTINCR HOXB-AS3 regulating hallmarks cancer, well roles CIP2A-BP diagnosis prognosis. discuss how AKT-174aa DDUP are involved anti-cancer underestimated potential targets.

Language: Английский

Citations

1
The copious capabilities of non-coding RNAs in cancer regulation, diagnosis and treatment DOI Creative Commons
Aideen McCabe, Oza Zaheed, Magdalina Derlipanska

et al.

Cancer Treatment and Research Communications, Journal Year: 2023, Volume and Issue: 37, P. 100768 - 100768

Published: Jan. 1, 2023

Globally, cancer is one of the leading causes mortality, accounting for 10 million deaths per year. Non-coding RNAs (ncRNAs) play integral and diverse roles in cancer, possessing ability to both promote oncogenesis impede tumor formation. This review discusses various microRNAs, transfer RNA-derived small RNAs, long non-coding lncRNA-derived microproteins progression prevention. We highlight diagnostic therapeutic potential these ncRNAs, with a particular focus on detection liquid biopsies targeting ncRNAs inhibitory molecules. Ultimately, biological functions cancer-associated as well development ncRNA-based technologies, are compelling areas further research, holding possibility revolutionizing treatment diagnosis.

Language: Английский

Citations

2