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TBX21 attenuates colorectal cancer progression via an ARHGAP29/RSK/GSK3β dependent manner

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Abstract

Purpose

Previous studies have shown that TBX21 (T-Box Transcription Factor 21) plays a vital role in coordinating multiple aspects of the immune response especially type 1 immune response as well as tumor progression. However, the function of TBX21 in colorectal cancer (CRC) remains unclear.

Methods

IHC to investigate TBX21 expression in CRC tissues. Cell proliferation and apoptosis assays to validate TBX21 function in vitro and in vivo. RNA-seq assay to explore target genes of TBX21. Human phospho-kinase array assay to explore down-stream signaling of TBX21.

Results

We disclosed that the expression of TBX21 was marked decreased in CRC versus normal tissue, and negatively correlated with CRC TNM stages. Surprisingly, we found that the CRC and normal cell lines show no TBX21 expression levels. Ectopic expression of TBX21 inhibited cell proliferation and promoted cell apoptosis in vitro. Moreover, RNA-sequence data first time showed that ARHGAP29 acts as the target gene of TBX21 to mediate down-stream signaling activation. Human phospho-kinase array data first time displayed that ectopic expression of TBX21 reduced kinase RSK and GSK3β activation. In contrast, knocked down the expression of TBX21 or ARHGAP29 alternatively abolished TBX21 mediated cell proliferation suppression, cell apoptosis enhancement and RSK/GSK3β activation. In addition, xenograft model studies demonstrated that TBX21 inhibits colorectal tumor progression via ARHGAP29/ RSK/ GSK3β signaling in vivo.

Conclusions

In summary, the aforementioned findings suggest a model of TBX21 in suppressing CRC progression. This may provide a promising target for CRC therapy.

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Data Availability Statement

The data are available for all study authors. The data sets used and analysed during the current study are available from the corresponding author on reasonable request.

Abbreviations

CRC:

Colorectal Cancer

TBX21:

T-Box Transcription Factor 21

ARHGAP29:

Rho GTPase activating protein 29

RSK:

Ribosomal S6 protein kinase

GSK3β:

Glycogen synthase kinase-3beta

CCK8:

Cell Counting Kit-8

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Funding

This work was supported by the National Natural Science Foundation of China (No. 82173192 to Wenzhi Shen), Shandong Provincial Natural Science Foundation (No. ZR2021QH113 to Yongming Huang), National Natural Science Foundation of China (No. 82203287 to Renle Du), Student Innovation Training Program of Jining Medical University (No. cx2021091 to Wenzhi Shen).

Author information

Authors and Affiliations

  1. Key Laboratory of Precision Oncology in Universities of Shandong, Institute of Precision Medicine, Jining Medical University, Jining, 272067, China

    Xinyu Jiang, Wenfei Du, Chenglong Yang, Xiaowen Yang, Xiaoyuan Zhang & Wenzhi Shen

  2. The Third Affiliated Hospital of Zunyi Medical University (The First People’s Hospital of Zunyi), Zunyi, 563000, China

    Shuying Wang

  3. Surgery Teaching and Research Section, Clinical Medical School, Jining Medical University, Jining, 272067, China

    Yifei Li & Xinzhuang Shen

  4. Department of Oncology, Jining Hospital of Traditional Chinese Medicine, Jining, 272000, China

    Jie Yao

  5. Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450052, China

    Renle Du

  6. Department of General Surgery, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, 272067, China

    Yongming Huang

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  1. Xinyu Jiang
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Contributions

JXY and SWZ designed the experiments, DWF, YCL, WSY and LYF prepared the materials and performed the experiments, SXZ and YXW analyzed the data, YJ and HYM helped to collect the CRC tumor tissue samples, SWZ wrote the manuscript, HYM, ZXY and SWZ repaired and prepared the manuscripts.

Corresponding authors

Correspondence to Xiaoyuan Zhang, Yongming Huang or Wenzhi Shen.

Ethics declarations

Ethics approval and consent to participate

The CRC tissue study was performed in accordance with Jining Medical University Medical Ethics Committee Guidelines, and approved by Jining Medical University Medical Ethics Committee. The animal experiments were performed in accordance with Jining Medical University Animal Welfare Guidelines, and approved by Jining Medical University Animal Ethics Committee.

Competing interests

The authors declare no competing interests.

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Jiang, X., Du, W., Yang, C. et al. TBX21 attenuates colorectal cancer progression via an ARHGAP29/RSK/GSK3β dependent manner. Cell Oncol. 46, 1269–1283 (2023). https://doi.org/10.1007/s13402-023-00809-6

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