# Study on the regulation mechanism of TBX5 gene and Gegen Qinlian decoction on colorectal cancer

**Authors:** Dong Chen, Yan Cai, Wencang Gao, Dexiang Pang, Senquan Yu

PMC · DOI: 10.3389/fonc.2025.1732015 · Frontiers in Oncology · 2026-01-14

## TL;DR

This study explores how the TBX5 gene and Gegen Qinlian Decoction influence colorectal cancer, identifying key genes and compounds that may aid in diagnosis and treatment.

## Contribution

The study reveals novel insights into TBX5's role in CRC and its interaction with GQD, including new gene and miRNA associations.

## Key findings

- TBX5 is overexpressed in CRC and linked to poorer survival rates.
- Several genes and immune cell types are associated with CRC prognosis.
- Molecular docking shows active compounds in GQD bind to TBX5.

## Abstract

TBX5 is a key protein regulated by the TGF-β/Smad3 pathway, which plays a significant role in colorectal cancer (CRC) development. This study aims to investigate the interplay between Gegen Qinlian Decoction (GQD), TBX5, and CRC mechanisms.

The Cancer Genome Atlas (TCGA-CRC) dataset from the TCGA database was utilized for the study. Differential expression analysis was conducted to identify differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs). Subsequently, analyses were performed focusing on TBX5, encompassing pan-cancer evaluation, protein-level expression assessment, and enrichment analysis. Correlation analyses were carried out to investigate the relationships between TBX5, clinical characteristics, prognosis, and key pathways in CRC. Furthermore, immune analysis, network construction, drug prediction, and molecular docking studies were conducted.

A total of 1,834 differentially expressed genes (DEGs) were identified in TCGA-CRC. TBX5 exhibited elevated expression levels in CRC compared to other cancer types and normal tissues, correlating with lower survival rates in the high TBX5 expression cohort. Additionally, SPTBN4, RP11-35N6.1, CHD5, SLC4A8, KLHL32, MAP2, and ATP8A2 were found to be prognostic markers for patient outcomes. Age, N, and M stages were identified as significant independent prognostic factors for CRC. Notably, there was a significant upregulation of cell stemness, epithelial-mesenchymal transition (EMT), and angiogenesis-related genes in the high TBX5 expression group. Furthermore, the prognostic significance of 10 immune cell types, including mast cells, myeloid-derived suppressor cells (MDSCs), and monocytes, was evident. Thirteen key miRNAs were identified, and an mRNA-miRNA-lncRNA regulatory network was constructed, revealing relationships such as TBX5-hsa-mir-1270-TMPO-AS1. Molecular docking analyses demonstrated favorable binding of active compounds like formononetin and cinnamic acid to TBX5.

Our findings suggested a potential association between GQD, TBX5-related genes, and CRC progression, which could provide valuable insights for the diagnosis and treatment of CRC.

## Linked entities

- **Genes:** TBX5 (T-box transcription factor 5) [NCBI Gene 6910], SPTBN4 (spectrin beta, non-erythrocytic 4) [NCBI Gene 57731], CHD5 (chromodomain helicase DNA binding protein 5) [NCBI Gene 26038], SLC4A8 (solute carrier family 4 member 8) [NCBI Gene 9498], KLHL32 (kelch like family member 32) [NCBI Gene 114792], MAP2 (microtubule associated protein 2) [NCBI Gene 4133], ATP8A2 (ATPase phospholipid transporting 8A2) [NCBI Gene 51761]
- **Proteins:** TBX5 (T-box transcription factor 5)
- **Chemicals:** formononetin (PubChem CID 5280378), cinnamic acid (PubChem CID 444539)
- **Diseases:** colorectal cancer (MONDO:0005575)

## Full-text entities

- **Genes:** SMAD3 (SMAD family member 3) [NCBI Gene 4088] {aka HSPC193, HsT17436, JV15-2, LDS1C, LDS3, MADH3}, MIR1270 (microRNA 1270) [NCBI Gene 100302179] {aka MIR1270-1, MIR1270-2, MIRN1270, hsa-mir-1270, hsa-mir-1270-1, mir-1270}, CHD5 (chromodomain helicase DNA binding protein 5) [NCBI Gene 26038] {aka CHD-5, PMNDS}, MAP2 (microtubule associated protein 2) [NCBI Gene 4133] {aka MAP-2, MAP2A, MAP2B, MAP2C}, ATP8A2 (ATPase phospholipid transporting 8A2) [NCBI Gene 51761] {aka ATP, ATPIB, CAMRQ4, IB, ML-1}, TMPO-AS1 (TMPO antisense RNA 1) [NCBI Gene 100128191], TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, KLHL32 (kelch like family member 32) [NCBI Gene 114792] {aka BKLHD5, KIAA1900, UG0030H05, dJ21F7.1}, SPTBN4 (spectrin beta, non-erythrocytic 4) [NCBI Gene 57731] {aka CMND, NEDHND, QV, SPNB4, SPTBN3}, SLC4A8 (solute carrier family 4 member 8) [NCBI Gene 9498] {aka NBC3, NDCBE}, TBX5 (T-box transcription factor 5) [NCBI Gene 6910] {aka HOS}
- **Diseases:** CRC (MESH:D015179), Cancer (MESH:D009369)
- **Chemicals:** cinnamic acid (MESH:C029010), formononetin (MESH:C007768)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

10 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12847017/full.md

## References

42 references — full list in the complete paper: https://tomesphere.com/paper/PMC12847017/full.md

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Source: https://tomesphere.com/paper/PMC12847017