Iranian Journal of Basic Medical Sciences, ( ISI ), Year (2025-1)

Title : ( Heterogeneous expression of long noncoding RNA i>RP11-109D20.2/i>: Insights into regulatory gene expression roles in colon cancer )

Authors: sara chitgaran , Reihaneh Alsadat Mahmoudian , Seyed Saeed Khatami , Fatemeh Nasrabadi , Ehsan Soltani , Amirnader Emami Razavi , Fatemeh Kamali , Ahmad Reza Bahrami , Maryam Moghaddam Matin , Moein Farshchian ,

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Abstract

Objective(s): Colorectal cancer is one of the deadliest cancers worldwide, which can be prevented and even cured by early diagnosis and more efficient treatment modalities. Comprehensive transcriptional analysis has highlighted the importance of lncRNAs in CRC tumorigenesis. In this study, we identified co-expressed lncRNA networks based on public RNA sequencing data for biomarker prediction in CRC and then verified the best candidate experimentally. Materials and Methods: Publicly available RNA-sequencing data (BioProject PRJEB27536) of CRC samples and normal adjacent tissues were reanalyzed using the DESeq2 package in R to find differentially expressed lncRNAs. Pathway enrichment and gene network analysis were accomplished using GSEA and WGCNA to identify potential functions of lncRNAs with possible roles in tumorigenesis pathways. Subsequently, the expression of RP11-109D20.2 (lnc-Duox2-1:1) was assessed in fresh/frozen tissues obtained from 46 CRC patients by quantitative RT-PCR. Results: A total of 17939 DElncRNAs were identified between CRC and normal tissues via bioinformatics analyses. A significant up-regulation of RP11-109D20.2 (48%) was observed in CRC samples. Functional enrichment analysis showed that RP11-109D20.2 was mainly related to pathways like phosphoric ester hydrolase, oxidoreductase, phosphoric diester hydrolase, and cyclic-nucleotide phosphodiester activities. Moreover, elevated expression of DUOX2 in tumors with high levels of RP11-109D20.2 suggests a link between these genes. Conclusion: Our data revealed that RP11-109D20.2 may have a considerable role in CRC progression. However, further functional analyses are essential to evaluate the probable role of RP11-109D20.2 as a potential diagnostic marker and its potential role in the dysregulation of cyclic nucleotide phosphodiesterase genes in CRC.

Keywords

, Biomarker, Colorectal cancer, Gene expression profiling, Long noncoding RNA RP11-109D20.2, RNA sequencing analysis