Unveiling the role of miR-137-3p/miR-296-5p/SERPINA3 signaling in colorectal cancer progression - integrative analysis of gene expression profiles and in vitro studies

Sep 24, 2026

Colorectal cancer (CRC) remains a major cause of death because metastasis drives poor outcomes, making molecular mechanisms essential for earlier intervention. Using integrated GEO gene expression datasets, the study performed differential expression, GO and KEGG enrichment, and prioritized SERPINA3 as a hub gene. In vitro assays assessed miR-137-3p/miR-296-5p/SERPINA3 effects on CRC migration, proliferation, EMT, and caspase-3/-9 activities, linking SERPINA3 to pro-metastatic and anti-apoptotic functions.

LanguageEnglish

CategoryResearch & Report

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Pages16

Reading Time40 min

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Abstract

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Results

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Introduction

Liu et al. BMC Medical Genomics (2023) 16:327 BMC Medical Genomics [https://doi.org/10.1186/s12920-023-01763-w](https://doi.org/10.1186/s12920-023-01763-w) RESEARCH Open Access Unveiling the role of miR-137-3p/miR-296- 5p/SERPINA3 signaling in colorectal cancer progression: integrative analysis of gene expression profiles and in vitro studies Huimin Liu 1†, Xingxing Wu2†, Dandan Wang 1†, Quanxi Li 1, Xin Zhang 1 and Liang Xu 1* Abstract Background Colorectal cancer (CRC) is a prevalent malignancy worldwide, with increasing incidence and mortality rates. Although treatment options have improved, CRC remains a leading cause of death due to metastasis. Early intervention can significantly improve patient outcomes, making it crucial to understand the molecular mechanisms underlying CRC metastasis. In this study, we performed bioinformatics analysis to identify potential genes associated with CRC metastasis. Methods We downloaded and integrated gene expression datasets (GSE89393, GSE100243, and GSE144259) from GEO database. Differential expression analysis was conducted, followed by Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The hub gene SERPINA3 was selected for further in vitro functional studies. Additionally, the role of miR-137-3p/miR-296-5p/ Serpin family A member 3 (SERPINA3) in CRC cell function was investigated using in vitro assays. Results Analysis of the gene expression datasets revealed differential ly expressed genes (DEGs) associated with CRC metastasis. GO analysis showed enrichment in biological processes such as blood coagulation regulation and wound healing. Cellular component analysis highlighted extracellular matrix components and secretory granules. Molecular function analysis identified activities such as serine-type endopeptidase inhibition and lipoprotein receptor binding. KEGG analysis revealed involvement in pathways related to complement and coagulation cascades, cholesterol metabolism, and immune responses. The common DEGs among the datasets were further investigated. We identified SERPINA3 as a hub gene associated with CRC metastasis. SERPINA3 exerted enhanced effects on migration, proliferation and epithelial-mesenchymal transition (EMT) and inhibitory effects on caspase-3/-9 activities in HT29 and SW620 cells. MiR-137-3p overexpression increased activities of caspase-3/-9, decreased migration and proliferation, and also repressed EMT in HT29 cells, which were obviously attenuated by SERPINA3 enforced overexpression. †Huimin Liu, Xingxing Wu and Dandan Wang contributed equally to this work. *Correspondence: Liang Xu [lygeyxxl@163.com](lygeyxxl@163.com) Full list of author information is available at the end of the article © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/l](http://creativecommons.org/l)icenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ([http://creativecommons.org/publicdomain/zero/1.0/](http://creativecommons.org/publicdomain/zero/1.0/)) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Liu et al. BMC Medical

FAQs

What datasets and analyses were used to identify candidate metastasis genes?

The study integrated GEO expression datasets (GSE89393, GSE100243, and GSE144259) and performed differential expression analysis followed by GO and KEGG enrichment to find metastasis-associated genes.

Why was SERPINA3 selected for further experiments?

SERPINA3 emerged as a hub gene consistently associated with CRC metastasis across the integrated gene expression analyses.

How does miR-137-3p/SERPINA3/SERPINA3 axis affect CRC cell behaviors?

MiR-137-3p overexpression increased caspase-3/-9 activity while reducing migration, proliferation, and EMT in HT29 cells, and these effects were attenuated when SERPINA3 was enforced.

Sep 24, 2026

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