Overexpression of Long Non-Coding RNA, LINC01748, Predicts Extracellular Matrix Remodeling in Colorectal Cancer Through Let-7b-5p/CTHRC1 Axis

Sep 22, 2026

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Colorectal cancer (CRC) remains a major cause of cancer-related deaths, and long non-coding RNAs are implicated in tumor regulation through microRNA-mediated gene expression control. This study examined LINC01748 in CRC and its interaction with the Let-7b-5p/CTHRC1 axis by analyzing TCGA RNA-seq data for differential lncRNAs, miRNAs, and mRNAs, predicting regulatory interactions, and performing network and functional enrichment analyses. RT-qPCR and western blotting assessed LINC01748, Let-7b-5p, and CTHRC1, with histopathology evaluating collagen density. LINC01748 showed CRC-specific upregulation, positively associated with CTHRC1 and inversely with Let-7b-5p, supporting a competing endogenous RNA role in extracellular matrix remodeling via this axis.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages15

Reading Time38 min

AccessFree to download

Introduction

Rationale for non-coding RNAs and ceRNA networks in CRC

Methods and Analyses

Differential expression, interaction prediction, and enrichment analyses

RT-qPCR, western blotting, and histopathology

Results

Differential RNAs and proposed ceRNA mechanism

Expression validation and correlation findings

Conclusion

Original Article [www.cmj.ac.kr](www.cmj.ac.kr) Overexpression of Long Non-Coding RNA, LINC01748, Predicts Extracellular Matrix Remodeling in Colorectal Cancer Through Let-7b-5p/CTHRC1 Axis Erfan Golestannejad1,2, Heidar Tayebinia1, Jamshid Karimi1, Amirnader Emami Razavi3, and Iraj Khodadadi1,4,* 1Department of Clinical Biochemistry, School of Medicine, Hamadan University of Medical Sciences, 2Student Research Committee, Hamadan University of Medical Sciences, Hamadan, 3Iran National Tumor Bank, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, 4Nutrition Health Research Center, Institute of Health Sciences and Technologies, Avicenna Health Research Institute, Hamadan University of Medical Sciences, Hamadan, Iran Colorectal cancer (CRC) is a leading cause of cancer-related deaths. Long non-coding RNAs are emerging as key regulators in cancer by modulating functions ofmicroRNAs thereby affecting expression of genes involved in the pathogenesis of cancers. Since the CTHRC1 gene (Collagen Triple‑Helix‑Repeat Containing‑1) encodes an extracellular matrix protein involved in collagen regulation and cell migration, this study investigated the role ofLINC01748 in CRC and its interaction with the Let-7b-5p/CTHRC1 axis. RNA sequencing data from The Cancer Genome Atlas database was analyzed to identify differentially expressed lncRNAs, miRNAs, and mRNAs in CRC. Interactions between LINC01748, miRNAs, and mRNAs were predicted, a protein-protein interaction network was constructed, and functional enrichment analysis was performed to reveal the biological activity of target genes. Additionally, the expression of LINC01748, Let-7b-5p, and CTHRC1 in CRC tissues and adjacent non-cancerous tissues were determined using RT-qPCR and western blotting. Collagen density was also evaluated by histopathological examination. 107 differentially expressed lncRNAs, 313 miRNAs, and 1,479 mRNAs were identified in CRC samples. Bioinformatics analysis indicated that LINC01748 may function as a competing endogenous‑RNA for Let-7b-5p, regulating CTHRC1 expression. RT-qPCR confirmed upregulation of LINC01748 and CTHRC1 and downregulation of Let-7b-5p in CRC. Significant positive correlation of LINC01748 with CTHRC1, and a negative correlation with Let-7b-5p were detected. Gene Ontology and KEGG pathway analysis suggested the involvement of LINC01748/Let-7b-5p/CTHRC1 axis in ECM organization and collagen content. This study revealed the role ofLINC01748 in the Let-7b-5p/CTHRC1 axis, highlighting its clinical significance in CRC. KeyWords: Colorectal Neoplasms; CTHRC1 Protein, Human; RNA, Long Noncoding; MicroRNAs; Extracellular Matrix This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ([http://creativecommons.org/licenses/by-nc/4.0](http://creativecommons.org/licenses/by-nc/4.0)) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Article History: Received December 12, 2025 Revised February 1, 2026 Accepted March 1, 2026 Corresponding Author: Iraj Khodadadi Department of Clinical Biochemistry, School of Medicine, Hamadan University of Medical Sciences, Hamadan 65178, Iran Tel: +98-81-38380572 Fax: +98-81-38380208 E-mail: [khodadadi@umsha.ac.ir](khodadadi@umsha.ac.ir) INTRODUCTION Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related deaths worldwide. It accounts for approximately 10% of all cancer diagnoses and is responsible for 9% of cancer fatalities, which remains the leading cause of cancer mortality.1 Multiple factors, including environmental, genetic, and epigenetic influences, may contribute to the development of CRC.2 Despite significant advancements in chemotherapy, surgical techniques, and the availability of vari- [https://doi.org/10.4068/cmj.2026.62.2.64](https://doi.org/10.4068/cmj.2026

FAQs

What did the study investigate in colorectal cancer?

It investigated whether LINC01748 regulates extracellular matrix remodeling in CRC through the Let-7b-5p/CTHRC1 axis, focusing on interactions among lncRNA, miRNA, and mRNA.

How were candidate non-coding RNAs and targets identified?

TCGA RNA-sequencing data were analyzed to find differentially expressed lncRNAs, miRNAs, and mRNAs in CRC, followed by interaction prediction, protein-protein network construction, and functional enrichment analysis.

What experimental methods validated the bioinformatics predictions?

RT-qPCR and western blotting measured LINC01748, Let-7b-5p, and CTHRC1 in CRC and adjacent non-cancerous tissues, and histopathological examination assessed collagen density.

Sep 22, 2026

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