Multiple regulatory events contribute to a widespread circular RNA downregulation in precancer and early stage of colorectal cancer development

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14310%2F25%3A00140949" target="_blank" >RIV/00216224:14310/25:00140949 - isvavai.cz</a>

Result on the web

<a href="https://biomarkerres.biomedcentral.com/articles/10.1186/s40364-025-00744-8" target="_blank" >https://biomarkerres.biomedcentral.com/articles/10.1186/s40364-025-00744-8</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1186/s40364-025-00744-8" target="_blank" >10.1186/s40364-025-00744-8</a>

Result language

angličtina

Original language name

Multiple regulatory events contribute to a widespread circular RNA downregulation in precancer and early stage of colorectal cancer development

Original language description

Background Early detection of colorectal cancer (CRC) significantly improves its management and patients' survival. Circular RNAs (circRNAs) are peculiar covalently closed transcripts involved in gene expression modulation whose dysregulation has been extensively reported in CRC cells. However, little is known about their alterations in the early phases of colorectal carcinogenesis. Methods In this study, we performed an integrative analysis of circRNA profiles in RNA-sequencing (RNA-Seq) data of 96 colorectal cancers, 27 adenomas, and matched adjacent mucosa tissues. We also investigated the levels of cognate linear transcripts and those of regulating RNA-binding proteins (RBPs). Levels of circRNA-interacting microRNAs (miRNAs) were explored by integrating data of small RNA-Seq performed on the same samples. Results Our results revealed a significant dysregulation of 34 circRNAs (paired adj. p &lt; 0.05), almost exclusively downregulated in tumor tissues and, prevalently, in early disease stages. This downregulation was associated with decreased expression of circRNA host genes and those encoding for RBPs involved in circRNA biogenesis, including NOVA1, RBMS3, and MBNL1. Guilt-by-association analysis showed that dysregulated circRNAs correlated with increased predicted activity of cell proliferation, DNA repair, and c-Myc signaling pathways. Functional analysis showed interactions among dysregulated circRNAs, RBPs, and miRNAs, which were supported by significant correlations among their expression levels. Findings were validated in independent cohorts and public datasets, and the downregulation of circLPAR1(2,3) and circLINC00632(5) was validated by ddPCR. Conclusions These results support that multiple altered regulatory mechanisms may contribute to the reduction of circRNA levels that characterize early colorectal carcinogenesis.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30204 - Oncology

Project

—

Continuities

S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2025

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

BIOMARKER RESEARCH

ISSN

2050-7771

e-ISSN

2050-7771

Volume of the periodical

13

Issue of the periodical within the volume

1

Country of publishing house

GB - UNITED KINGDOM

Number of pages

18

Pages from-to

1-18

UT code for WoS article

001427970300001

EID of the result in the Scopus database

2-s2.0-85218502584