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Homeobox B9 Promotes Colon Cancer Progression by Targeting SRSF3

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Abstract

Background

Homeobox B9 (HOXB9) is one of the HOX family of transcription factors that are essential for cancer development and embryonic growth. However, the clinical importance and biological involvement of HOXB9 in colon cancer (CC) are not adequately understood.

Aims

To investigate whether HOXB9 participates in the proliferation, invasion, and migration of CC.

Methods

This study investigated the function and clinical significance of HOXB9 mRNA and protein expression in CC. Furthermore, overexpression and knockdown experiments of HOXB9 were developed to explore their effects on CC cell transwell and proliferation. Moreover, a molecular mechanism of HOXB9 regulate serine/arginine-rich splicing factor 3 (SRSF3) was explored.

Results

HOXB9 expression was higher in CC cells and tissues at both the mRNA and protein levels. Poor survival in CC patients was significantly connected with high HOXB9 expression, which was also strongly associated with the TNM stage and lymph node metastases. Furthermore, in vitro CC cell proliferation, transwell were markedly aided by HOXB9 overexpression. Contrarily, HOXB9 knockdown had the reverse result and inhibited the formation of xenograft tumors in naked mice. Gene set enrichment analysis (GSEA) revealed a correlation between high HOXB9 expression and spliceosomes. JASPAR and GEPIA2.0, in addition to CHIP and dual-luciferase reporting assays, confirmed that HOXB9 targets the promoter of SRSF3 to enhance its expression. We also found that SRSF3 knockdown eliminated HOXB9 from cell proliferation and transwell.

Conclusion

We characterized the function and mechanism of HOXB9 in regulating colon cancer growth, suggesting a novel molecular approach for colon cancer-targeted therapy.

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Acknowledgment

The authors thank the contributors to GEPIA 2.0 for contributing shared sequencing datasets for open access. Also, the GSEA database has provided us with new ideas to search for signaling pathway mechanisms, and furthermore, we are grateful to JASPAR for providing us with convenient information on transcription factor-related data.

Funding

This research was supported by the National Natural Science Foundation of China, No .81860432 (1) and the Natural Science Foundation of Jiangxi Province (20171BAB205064).

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Authors and Affiliations

  1. Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, People’s Republic of China

    Lebin Yuan, Fei Cheng, Zhao Wu, Xiaodong Li & Wei Shen

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  1. Lebin Yuan
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  5. Wei Shen
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Contributions

WS conducted the study design. YL drafted the manuscript, CF participated in the coordination of the study and acted as technical advisor, WZ performed the analysis and collected the samples, LX performed the statistical analysis of the data, with equal contributions from YL and CF. CF, WZ and XD revised the manuscript. All authors reviewed and approved the final manuscript.

Corresponding author

Correspondence to Wei Shen.

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Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

This study was approved by Ethics Committee of the Second Affiliated Hospital of Nanchang University (Nanchang, China).

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Each patient had signed the informed consent.

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Yuan, L., Cheng, F., Wu, Z. et al. Homeobox B9 Promotes Colon Cancer Progression by Targeting SRSF3. Dig Dis Sci 68, 3324–3340 (2023). https://doi.org/10.1007/s10620-023-07977-3

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